Transforming Growth Factor β‐Activated Kinase 1 Regulates Mesenchymal Stem Cell Proliferation Through Stabilization of Yap1/Taz Proteins
This study reveals a novel pathway controlling BMMSC proliferation and suggests a useful method to improve the therapeutic effect of BMMSC transplantation.Stem Cells2019 (Source: Stem Cells)
Source: Stem Cells - November 18, 2019 Category: Stem Cells Authors: Yuta Onodera, Takeshi Teramura, Toshiyuki Takehara, Kanji Fukuda Tags: Tissue ‐Specific Stem Cells Source Type: research

Induced Pluripotent Stem Cells Attenuate Endothelial Leakage in Acute Lung Injury via Tissue Inhibitor of Metalloproteinases ‐1 to Reduce Focal Adhesion Kinase Activity
This study reports that induced pluripotent stem cells reduce the endothelial cell permeability by reversing lipopolysacchari de‐induced suppression of vascular endothelial cadherin in pulmonary endothelium. This study further suggested that induced pluripotent stem cells downregulate the expression of pFAK‐Tyr397 and Snail via tissue inhibitor of metalloproteinases‐1 in lipopolysaccharide‐induced acute lung injury . AbstractInduced pluripotent stem cells (iPSCs) can reduce the severity of endotoxin ‐induced acute lung injury (ALI). However, the interaction between iPSCs and vascular endothelium remains unclear. ...
Source: Stem Cells - November 18, 2019 Category: Stem Cells Authors: Vincent Yi ‐Fong Su, Shih‐Hwa Chiou, Chi‐Shiuan Lin, Min‐Hsiang Mo, Kuang‐Yao Yang Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line ‐ and method‐dependent
Three human iPSC lines were differentiated to retinal organoids using differentiation protocols activating either BMP4 or IGF1 signalling pathways. All cell lines were able to generate retinal organoids. However, the two differentiation approaches produced bias toward certain retinal cell types within the organoids, which was iPSC line ‐ and method‐dependent. AbstractInduced pluripotent stem cell (iPSC) ‐derived retinal organoids provide a platform to study human retinogenesis, disease modelling and compound screening. Whilst retinal organoids may represent tissue structures with greater physiological relevance to th...
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Valeria Chichagova, Gerrit Hilgen, Ali Ghareeb, Maria Georgiou, Madeleine Carter, Evelyne Sernagor, Majlinda Lako, Lyle Armstrong Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Hes1 Regulates Anagen Initiation and Hair Follicle Regeneration through Modulation of Hedgehog Signaling
Working model: By modulating ciliary function, Hes1 potentiates Shh signaling in anagen initiation, which allows sufficient signaling strength to expand the hair germ and replenish HFSCs to maintain the hair cycle. AbstractAdult hair follicles undergo repeated cycling of regression (catagen), resting (telogen), and growth (anagen), which is maintained by hair follicle stem cells (HFSCs). The mechanism underlying hair growth initiation and HFSC maintenance is not fully understood. Here, by epithelial deletion ofHes1, a major Notch downstream transcriptional repressor, we found that hair growth is retarded but the hair cycle...
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Wei ‐Jeng Suen, Shao‐Ting Li, Liang‐Tung Yang Tags: Tissue ‐Specific Stem Cells Source Type: research

Tissue Repair Brakes: A Common Paradigm in the Biology of Regeneration
Cell identity maintenance, at all stages of life, is modulated by inhibitory signals from the surrounding cellular environment. Stress ‐mediated suppression of these signals, such as after a lesion, may lead fully mature differentiated specialized cells to change their function, thus fostering regeneration of injured tissue. Controlling this cellular plasticity could prove crucial to developing new therapies to treat degenerative diseases. AbstractTo date, most attention on tissue regeneration has focused on the exploration of positive cues promoting or allowing the engagement of natural cellular restoration upon injury....
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Valentina Cigliola, Luiza Ghila, Simona Chera, Pedro L. Herrera Tags: Regenerative Medicine Source Type: research

Wnt5a promotes differentiation and development of adult ‐born neurons in the hippocampus by non‐canonical Wnt signaling
This study demonstrates that Wnt5a is a neurogenic factor that promotes neuronal differentiation and morphological development of adult ‐born neurons in the hippocampus. Results indicate that Wnt5a signals through CaMKII to induce neuronal differentiation, and induces dendritic development of newborn neurons through Wnt/JNK and Wnt/CaMKII pathways. Together, these findings identify Wnt5a as an endogenous non‐canonical Wnt ligand regulating adult hippocampal neurogenesis. (Source: Stem Cells)
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Sebastian B. Arredondo, Fernanda G. Guerrero, Andrea Herrera ‐Soto, Joaquin Jensen‐Flores, Daniel B. Bustamante, Alejandro Oñate‐Ponce, Pablo Henny, Manuel Varas‐Godoy, Nibaldo C. Inestrosa, Lorena Varela‐Nallar Tags: Tissue ‐Specific Stem Cells Source Type: research

KLF2+ stemness maintains human mesenchymal stem cells in bone regeneration
This study provides insight into the stemness‐directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the applicatio n of KLF2+ hMSC/HUVEC ‐laden GelMA hydrogel in vascular network bioengineering and bone regeneration.© AlphaMed Press 2019Significance StatementKLF2 was creatively put forward as a novel marker in vitro for MSCs to investigate the osteogenesis and angiogenesis between KLF2+ MSCs and ECs. We demonstrated there was a synergistic strategy to help readers understand the process of intercellular interaction between hMSCs and H...
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Ying Zhou, Chao Liu, Jianxiang He, Lingqing Dong, Huiyong Zhu, Bin Zhang, Xiaoxia Feng, Wenjian Weng, Kui Cheng, Mengfei Yu, Huiming Wang Tags: Regenerative Medicine Source Type: research

A histone deacetylase 7 ‐derived peptide promotes vascular regeneration via facilitating 14‐3‐3γ phosphorylation
This study provides evidence that sORFs can be alternatively translated and the derived peptides may play an important role in physiological processes including vascular remodeling.© AlphaMed Press 2019Significance StatementHistone deacetylase 7 (HDAC7) plays a pivotal role in the maintenance of the endothelial integrity. Short open reading frames (sORFs) exist within the 5 ′ terminal non‐coding area of Hdac7 mRNA. It remains unclear whether these sORFs contribute to HADC7 functions. In this study, we demonstrated that a 7‐amino acid peptide could be translated from a sORF. This peptide could act as phosphat...
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Junyao Yang, Ana Moraga, Jing Xu, Yue Zhao, Peiyi Luo, Ka Hou Lao, Andriana Margariti, Qiang Zhao, Wei Ding, Gang Wang, Min Zhang, Lei Zheng, Zhongyi Zhang, Yanhua Hu, Wen Wang, Lisong Shen, Alberto Smith, Ajay M Shah, Qian Wang, Lingfa Tags: Tissue ‐Specific Stem Cells Source Type: research

CD10 expression identifies a subset of human perivascular progenitor cells with high proliferation and calcification potentials
Sonic hedgehog (SHH)/GLI1/CD10 signaling in the perivascular niche (Figure  #stem3112-supitem-0008S8). SHH secreted in the perivascular niche induces GLI1 and CD10 expression. CD10 can upregulate CCND2 expression via ERK1/2 and stimulate NELL1 expression via NF ‐κB, which leads to self‐renewal and high osteogenic potential in human adventitial cells. AbstractThetunica adventitia ensheathes arteries and veins and contains presumptive mesenchymal stem cells (MSCs) involved in vascular remodeling. We show here that a subset of human adventitial cells express the CD10/CALLA cell surface metalloprotease. Both CD1...
Source: Stem Cells - November 13, 2019 Category: Stem Cells Authors: Lijun Ding, Bianca Vezzani, Nusrat Khan, Jing Su, Lu Xu, Guijun Yan, Yong Liu, Ruotian Li, Anushri Gour, Zhenyu Diao, Yali Hu, Zhongzhou Yang, W. Reef Hardy, Aaron W. James, Haixiang Sun, Bruno P éault Tags: Tissue ‐Specific Stem Cells Source Type: research

Unlocking the paradoxical endogenous stem cell response after spinal cord injury: Concise review
Response of spinal cord ependymal stem cells to spinal cord injury. A, Glutamate stimulates neural stem/progenitor cell (NSPC) proliferation and enhances survival through AMPA receptor activation. B, M1 macrophages increase pro ‐inflammatory cytokine mRNA expression in NSPCs and enhance proliferation through MAPK‐Sox2 signaling. M2 macrophages increase anti‐inflammatory cytokine mRNA expression in NSPCs, reduce proliferation, and increase neuronal differentiation. C, Myelin‐derived inhibitory proteins limit NSPC pr oliferation and neuronal differentiation via NgR1 signaling. D, NSPCs maintain a high endogenous leve...
Source: Stem Cells - November 9, 2019 Category: Stem Cells Authors: Laureen D. Hachem, Andrea J. Mothe, Charles H. Tator Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

The role of TRIM family proteins in the regulation of cancer stem cell self ‐renewal: Concise review
The tripartite ‐motif (TRIM) family of proteins is involved in a variety of cellular functions and biological processes that facilitate acquisition or maintenance of stem cell self‐renewal. AbstractThe tripartite ‐motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING‐finger E3 ubiquitin ligases. Members of this family are characterized by an N‐terminal TRIM motif containing one RING‐finger domain, one or two zinc‐finger domains called B boxes (B1 box and B2 box), and a coiled‐coil region. The TRIM motif can be found in isolation or in combination with a variet...
Source: Stem Cells - November 9, 2019 Category: Stem Cells Authors: Anna Maria Jaworska, Nikola Agata Wlodarczyk, Andrzej Mackiewicz, Patrycja Czerwinska Tags: CANCER STEM CELLS Source Type: research

Unlocking the paradoxical endogenous stem cell response after spinal cord injury: Concise review
Response of spinal cord ependymal stem cells to spinal cord injury. A, Glutamate stimulates neural stem/progenitor cell (NSPC) proliferation and enhances survival through AMPA receptor activation. B, M1 macrophages increase pro ‐inflammatory cytokine mRNA expression in NSPCs and enhance proliferation through MAPK‐Sox2 signaling. M2 macrophages increase anti‐inflammatory cytokine mRNA expression in NSPCs, reduce proliferation, and increase neuronal differentiation. C, Myelin‐derived inhibitory proteins limit NSPC pr oliferation and neuronal differentiation via NgR1 signaling. D, NSPCs maintain a high endogenous leve...
Source: Stem Cells - November 9, 2019 Category: Stem Cells Authors: Laureen D. Hachem, Andrea J. Mothe, Charles H. Tator Tags: TISSUE ‐SPECIFIC STEM CELLS Source Type: research

The role of TRIM family proteins in the regulation of cancer stem cell self ‐renewal: Concise review
The tripartite ‐motif (TRIM) family of proteins is involved in a variety of cellular functions and biological processes that facilitate acquisition or maintenance of stem cell self‐renewal. AbstractThe tripartite ‐motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING‐finger E3 ubiquitin ligases. Members of this family are characterized by an N‐terminal TRIM motif containing one RING‐finger domain, one or two zinc‐finger domains called B boxes (B1 box and B2 box), and a coiled‐coil region. The TRIM motif can be found in isolation or in combination with a variet...
Source: Stem Cells - November 9, 2019 Category: Stem Cells Authors: Anna Maria Jaworska, Nikola Agata Wlodarczyk, Andrzej Mackiewicz, Patrycja Czerwinska Tags: CANCER STEM CELLS Source Type: research

Adenomatous Polyposis Coli as a Major Regulator of Human Embryonic Stem Cells Self ‐Renewal
Familial adenomatous polyposis (FAP) ‐human embryonic stem cells (hESCs) carrying a germlineadenomatous polyposis coli (APC) mutation infected with a Wnt/ β‐catenin signaling reporter were subjected to (CRISPR/Cas9) in order to generateAPC“second‐hit” mutations.APC targeting resulted in robust Wnt/ β‐catenin signaling activation, loss of pluripotency, and mesendodermal differentiation, indicating that APC has a critical role in the maintenance of hESC self‐renewal. AbstractHuman embryonic stem cells (hESCs) provide an essential tool to investigate early human development, study disease patho...
Source: Stem Cells - November 4, 2019 Category: Stem Cells Authors: Livia Preisler, Dalit Ben ‐Yosef, Yoav Mayshar Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Extracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche
This study proves that fibroblast ‐derived EVs transport epidermal growth factor activity, such as amphiregulin, thus, they represent a novel way of intercellular signal transmission mechanism for normal ISCs. AbstractExtracellular vesicles (EV) are membrane ‐surrounded vesicles that represent a novel way of intercellular communication by carrying biologically important molecules in a concentrated and protected form. The intestinal epithelium is continuously renewed by a small proliferating intestinal stem cell population (ISC), residing at the bottom of the intestinal crypts in a specific microenvironment, the stem ce...
Source: Stem Cells - November 1, 2019 Category: Stem Cells Authors: Ádám Oszvald, Zsuzsanna Szvicsek, Gyöngyvér Orsolya Sándor, Andrea Kelemen, András Áron Soós, Krisztina Pálóczi, Attila Bursics, Kristóf Dede, Tamás Tölgyes, Edit I. Buzás, Anikó Zeöld, Zoltán Wiener Tags: Tissue ‐Specific Stem Cells Source Type: research

Integrative and perturbation based analysis of the transcriptional dynamics of TGF β/BMP system components in transition from embryonic stem cells to neural progenitors
Schematic illustration of a systems level approach to dissect the transcriptional and intra ‐dependent network of the TGFβ/BMP signaling pathway in embryonic stem cells that gradually differentiate to neural progenitors. AbstractCooperative actions of extrinsic signals and cell ‐intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by Transforming Growth Factor type β (TGFβ) family ligands (eg, Bone Morphogenetic Proteins [BMPs] and Activins/Nodal) exerts cell‐type specific and context‐ dependent transcriptional changes...
Source: Stem Cells - November 1, 2019 Category: Stem Cells Authors: Ruben Dries, Agata Stryjewska, Kathleen Coddens, Satoshi Okawa, Tineke Notelaers, Judith Birkhoff, Mike Dekker, Catherine M. Verfaillie, Antonio Sol, Eskeatnaf Mulugeta, Andrea Conidi, Frank G. Grosveld, Danny Huylebroeck Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Extracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche
This study proves that fibroblast ‐derived EVs transport epidermal growth factor activity, such as amphiregulin, thus, they represent a novel way of intercellular signal transmission mechanism for normal ISCs. AbstractExtracellular vesicles (EV) are membrane ‐surrounded vesicles that represent a novel way of intercellular communication by carrying biologically important molecules in a concentrated and protected form. The intestinal epithelium is continuously renewed by a small proliferating intestinal stem cell population (ISC), residing at the bottom of the intestinal crypts in a specific microenvironment, the stem ce...
Source: Stem Cells - November 1, 2019 Category: Stem Cells Authors: Ádám Oszvald, Zsuzsanna Szvicsek, Gyöngyvér Orsolya Sándor, Andrea Kelemen, András Áron Soós, Krisztina Pálóczi, Attila Bursics, Kristóf Dede, Tamás Tölgyes, Edit I. Buzás, Anikó Zeöld, Zoltán Wiener Tags: Tissue ‐Specific Stem Cells Source Type: research

Integrative and perturbation based analysis of the transcriptional dynamics of TGF β/BMP system components in transition from embryonic stem cells to neural progenitors
Schematic illustration of a systems level approach to dissect the transcriptional and intra ‐dependent network of the TGFβ/BMP signaling pathway in embryonic stem cells that gradually differentiate to neural progenitors. AbstractCooperative actions of extrinsic signals and cell ‐intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by Transforming Growth Factor type β (TGFβ) family ligands (eg, Bone Morphogenetic Proteins [BMPs] and Activins/Nodal) exerts cell‐type specific and context‐ dependent transcriptional changes...
Source: Stem Cells - November 1, 2019 Category: Stem Cells Authors: Ruben Dries, Agata Stryjewska, Kathleen Coddens, Satoshi Okawa, Tineke Notelaers, Judith Birkhoff, Mike Dekker, Catherine M. Verfaillie, Antonio Sol, Eskeatnaf Mulugeta, Andrea Conidi, Frank G. Grosveld, Danny Huylebroeck Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Concise Review: Deciphering retinal diseases through the generation of three dimensional stem cell ‐derived organoids
AbstractThree ‐dimensional (3D) retinal organoids, in vitro tissue structures derived from self‐organizing cultures of differentiating human embryonic stem cells or induced pluripotent stem cells, could recapitulate some aspects of the cytoarchitectural structure and function of the retina in vivo. 3D retinal organoids display huge potential for the investigation of the pathogenesis of monogenic hereditary eye diseases that are related to the malfunction or degeneration of photoreceptors or retinal ganglion cells by providing an effective in vitro tool with multiple applications. In combination with rec ent genome edit...
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Ana Artero Castro, Francisco Javier Rodr íguez Jimenez, Pavla Jendelova, Slaven Erceg Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Concise review: Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells
Schematic representation of the key processes of lipid metabolism that could be targeted in cancer stem cells (CSCs) and their associated metabolic regulators. AbstractEmerging evidences in cancer metabolomics have identified reprogrammed metabolic pathways to be a major hallmark of cancer, among which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Malini Visweswaran, Frank Arfuso, Sudha Warrier, Arun Dharmarajan Tags: CANCER STEM CELLS Source Type: research

Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell ‐derived retinal organoids
In this study, we investigated the impact of stage‐specific addition of retinoic acid (RA), 9‐cis‐retinal, 11‐cis‐retinal, levod opa (l‐DOPA), triiodothyronine (T3), and γ‐secretase inhibitor ((2S)‐N‐[(3,5‐Difluorophenyl)acetyl]‐l‐alanyl‐2‐phenyl]glycine1,1‐dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 12 0 of differentiation enhanced the generation of rod and S‐cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 ...
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Darin Zerti, Birthe Dorgau, Majed Felemban, Ali E. Ghareeb, Min Yu, Yuchun Ding, Natalio Krasnogor, Majlinda Lako Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Concise Review: Deciphering retinal diseases through the generation of three dimensional stem cell ‐derived organoids
AbstractThree ‐dimensional (3D) retinal organoids, in vitro tissue structures derived from self‐organizing cultures of differentiating human embryonic stem cells or induced pluripotent stem cells, could recapitulate some aspects of the cytoarchitectural structure and function of the retina in vivo. 3D retinal organoids display huge potential for the investigation of the pathogenesis of monogenic hereditary eye diseases that are related to the malfunction or degeneration of photoreceptors or retinal ganglion cells by providing an effective in vitro tool with multiple applications. In combination with rec ent genome edit...
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Ana Artero Castro, Francisco Javier Rodr íguez Jimenez, Pavla Jendelova, Slaven Erceg Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Concise review: Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells
Schematic representation of the key processes of lipid metabolism that could be targeted in cancer stem cells (CSCs) and their associated metabolic regulators. AbstractEmerging evidences in cancer metabolomics have identified reprogrammed metabolic pathways to be a major hallmark of cancer, among which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Malini Visweswaran, Frank Arfuso, Sudha Warrier, Arun Dharmarajan Tags: CANCER STEM CELLS Source Type: research

Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell ‐derived retinal organoids
In this study, we investigated the impact of stage‐specific addition of retinoic acid (RA), 9‐cis‐retinal, 11‐cis‐retinal, levod opa (l‐DOPA), triiodothyronine (T3), and γ‐secretase inhibitor ((2S)‐N‐[(3,5‐Difluorophenyl)acetyl]‐l‐alanyl‐2‐phenyl]glycine1,1‐dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 12 0 of differentiation enhanced the generation of rod and S‐cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 ...
Source: Stem Cells - October 31, 2019 Category: Stem Cells Authors: Darin Zerti, Birthe Dorgau, Majed Felemban, Ali E. Ghareeb, Min Yu, Yuchun Ding, Natalio Krasnogor, Majlinda Lako Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Inherited cardiac diseases, pluripotent stem cells and genome editing combined – the past, present and future
Key phenotypic features of inherited cardiac diseases that are seen in patients are often detected in the corresponding hiPSC ‐derived cardiomyocytes (past). Now (present), genome editing tools enable disease genotype–phenotype relationships to be investigated. In the future, this could aid in identifying both pathogenic and disease‐modifying genetic variants, and potentially contribute to improvements in diagnosis, prognosis and treatment of patients. AbstractResearch on mechanisms underlying monogenic cardiac diseases such as primary arrhythmias and cardiomyopathies has until recently been hampered by inherent ...
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Lettine Brink, Catarina Grandela, Christine L. Mummery, Richard P. Davis Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Contributions of Single ‐Cell Approaches for Probing Heterogeneity and Dynamics of Neural Progenitors Throughout Life: Concise Review
Neural stem cells (NSCs) within the periventricular region underline the germinal activity of the forebrain at both pre ‐ and post‐natal times. This review summarizes recent contribution of single cell approaches, i.e., clonal fate mapping and single cell transcriptomics, to our understanding of NSCs heterogeneity as well as of their evolving spatial and temporal identities. AbstractDevelopment of the forebrain occurs in a stepwise manner from a pool of neural progenitors (NPs), which differs over space and time to produce distinct progenies. The sequence of events leading to the generation of the exquisite complexity ...
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Guillaume Marcy, Olivier Raineteau Tags: Tissue ‐Specific Stem Cells Source Type: research

A Preview of Selected Articles
STEM CELLS, Volume 37, Issue 11, Page 1369-1371, November 2019. (Source: Stem Cells)
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Stuart P. Atkinson Tags: Previews Source Type: research

Cover Image
Cover Art: Serial FLAIR magnetic resonance images obtained at 1 month (left) and 24 months (right) of onset in an ischemic stroke patient treated with bone marrow ‐derived autologous mononuclear cells. See Vahidy et al. beginning on page1481. (Source: Stem Cells)
Source: Stem Cells - October 30, 2019 Category: Stem Cells Tags: Cover Image Source Type: research

Issue Information
STEM CELLS, Volume 37, Issue 11, Page i-viii, November 2019. (Source: Stem Cells)
Source: Stem Cells - October 30, 2019 Category: Stem Cells Tags: Issue Information Source Type: research

Epigenetic Regulation of Transition Among Different Pluripotent States: Concise Review
Different pluripotent states exist and have been established in vitro, including two ‐cell‐like cells, expanded potential stem cells and extended pluripotent stem cells, naive embryonic stem cells, and primed epiblast stem cells. Compared with postimplantation state, preimplantation state exhibits a more open chromatin structure, marked by DNA hypomethylation and enriched active histone modifications. AbstractThe extraordinary progress of pluripotent stem cell research provides a revolutionary avenue to understand mammalian early embryonic development. Besides well ‐established conventional mouse and human embryonic ...
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Ting Geng, Donghui Zhang, Wei Jiang Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

The role of TRIM family proteins in the regulation of cancer stem cell self ‐renewal
The tripartite ‐motif (TRIM) family of proteins is involved in a variety of cellular functions and biological processes that facilitate acquisition or maintenance of stem cell self‐renewal. AbstractThe tripartite ‐motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING‐finger E3 ubiquitin ligases. Members of this family are characterized by an N‐terminal TRIM motif containing one RING‐finger domain, one or two zinc‐finger domains called B boxes (B1 box and B2 box), and a coiled‐coil region. The TRIM motif can be found in isolation or in combination with a variet...
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Anna Maria Jaworska, Nikola Agata Wlodarczyk, Andrzej Mackiewicz, Patrycja Czerwinska Tags: Cancer Stem Cells Source Type: research

Inherited cardiac diseases, pluripotent stem cells and genome editing combined – the past, present and future
Key phenotypic features of inherited cardiac diseases that are seen in patients are often detected in the corresponding hiPSC ‐derived cardiomyocytes (past). Now (present), genome editing tools enable disease genotype–phenotype relationships to be investigated. In the future, this could aid in identifying both pathogenic and disease‐modifying genetic variants, and potentially contribute to improvements in diagnosis, prognosis and treatment of patients. AbstractResearch on mechanisms underlying monogenic cardiac diseases such as primary arrhythmias and cardiomyopathies has until recently been hampered by inherent ...
Source: Stem Cells - October 30, 2019 Category: Stem Cells Authors: Lettine Brink, Catarina Grandela, Christine L. Mummery, Richard P. Davis Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells: Concise review
Schematic representation of the key processes of lipid metabolism that could be targeted in CSCs and their associated metabolic regulators. AbstractEmerging evidences in cancer metabolomics have identified reprogrammed metabolic pathways to be a major hallmark of cancer, amongst which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Malini Visweswaran, Frank Arfuso, Sudha Warrier, Arun Dharmarajan Tags: Cancer Stem Cells Source Type: research

Unlocking the Paradoxical Endogenous Stem Cell Response after Spinal Cord Injury
Response of spinal cord ependymal stem cells to spinal cord injury. A, Glutamate stimulates neural stem/progenitor cell (NSPC) proliferation and enhances survival through AMPA receptor activation. B, M1 macrophages increase pro ‐inflammatory cytokine mRNA expression in NSPCs and enhance proliferation through MAPK‐Sox2 signaling. M2 macrophages increase anti‐inflammatory cytokine mRNA expression in NSPCs, reduce proliferation, and increase neuronal differentiation. C, Myelin‐derived inhibitory proteins limit NSPC pr oliferation and neuronal differentiation via NgR1 signaling. D, NSPCs maintain a high endogenous leve...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Laureen D. Hachem, Andrea J. Mothe, Charles H. Tator Tags: Tissue ‐Specific Stem Cells Source Type: research

Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells
The formin mDia2 is localized to the nucleus of the mesenchymal stem cell, while mDia1 is restricted to the cytoplasm. mDia2 is critical to function of the actin ‐lamin nucleoskeleton where it inhibits lineage commitment. When mDia2 is deficient, the lamin B1 nucleoskeleton is disrupted, activating osteogenesis, but not adipogenesis. AbstractNuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow derived MSCs, the principal diaphanous ‐related formin Diaph3 (mDia2) is present in the nucleus and regulates intranuclear actin polymerization, while Diaph1 (mDia1) is localized...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Jeyantt S. Sankaran, Buer Sen, Amel Dudakovic, Christopher R. Paradise, Tony Perdue, Zhihui Xie, Cody McGrath, Maya Styner, Joshua Newberg, Gunes Uzer, Andre J. Wijnen, Janet Rubin Tags: Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics Source Type: research

Proteasome Activation by Insulin ‐like Growth Factor‐1/Nuclear Factor Erythroid 2‐related Factor 2 Signaling Promotes Exercise‐induced Neurogenesis
This study shows that voluntary exercise causes hippocampal proteasome activation to improve adult neural progenitor cells activity. Mechanistically, exercise induces the increase of insulin like growth factor 1 (IGF ‐1) in serum and hippocampus, which in turn triggers the nuclear translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2) to promote the expression of the key proteasome subunit PSMB5 to enhance adult neurogenesis. This finding reveals novel insights into the modulation of adult neuro genesis through proteasome activation, which could be achieved by targeting the IGF‐1/Nrf2 signaling pathway. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Xiaojie Niu, Yunhe Zhao, Na Yang, Xuechun Zhao, Wei Zhang, Xiaowen Bai, Ang Li, Wulin Yang, Li Lu Tags: Tissue ‐Specific Stem Cells Source Type: research

Tunable hydrogels for mesenchymal stem cell delivery: integrin ‐induced transcriptome alterations and hydrogel optimization for human wound healing
PEG ‐8‐norbornene (PEG‐8‐Nb) and the peptide cross‐linker GCRDVPMS↓MRGGDRCG (that degrades in response to MMP ‐1, 2, 3, 7, and 9) were reacted, with the aid of the photoinitiator LAP, in the presence of MSC to form 3D hydrogel cultures. Parallel cultures were established similarly but with the addition of cysteine‐functionalized integrin‐binding small molecules, RGDS or LLP2A. MSC transcriptome profil ing revealed that hydrogel cultures altered the expression of genes important for extracellular matrix production, glycosylation, metabolism, and gene epigenetic regulation. AbstractTherapeutic applicatio...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Alina I. Marusina, Alexander A. Merleev, Jesus I. Luna, Laura Olney, Nathan E. Haigh, Daniel Yoon, Chen Guo, Elisa M. Ovadia, Michiko Shimoda, Guillaume Luxardi, Sucharita Boddu, Nelvish N. Lal, Yoshikazu Takada, Kit S. Lam, Ruiwu Liu, R. R Tags: Regenerative Medicine Source Type: research

Mesenchymal stem cells alleviate AQP ‐4‐dependent glymphatic dysfunction and improve brain distribution of antisense oligonucleotides in BACHD mice
In this study, the glymphatic system was found to be pivotal in ASO distribution. Moreover, an intravenously injection of MSCs (IV ‐MSC) rescued the loss of AQP‐4 in an HD mouse model. Since AQP‐4 is a critical channel in the brain glymphatic system, more ASOs were found in the brain tissue and a lower mutant HTT level was present in an HD mouse model with an IV‐MSC injection. In summary, IV‐MSC may be a potential the rapy to enhance ASO distribution efficiency and promote its therapeutic outcome in HD patients. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Teng ‐teng Wu, Feng‐juan Su, Yan‐qing Feng, Bin Liu, Ming‐yue Li, Feng‐yin Liang, Ge Li, Xue‐jiao Li, Yu Zhang, Zhong‐qiong Cai, Zhong Pei Tags: Regenerative Medicine Source Type: research

Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells
This study demonstrates that Canonical Wnt signaling promotes cardiac pacemaker lineage from Flk1+/PdgfR ‐α+ cardiac progenitors. Thede novo pacemaker cells exhibit hallmark features of native cardiac pacemaker cells, attesting to their therapeutic potential for cardiac rhythm ‐related diseases. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Wenbin Liang, Pengcheng Han, Elizabeth H. Kim, Jordan Mak, Rui Zhang, Angelo G. Torrente, Joshua I. Goldhaber, Eduardo Marb án, Hee Cheol Cho Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Dynamic regulation of connexins in stem cell pluripotency
Schematic model depicting expression levels of connexins relative to the pluripotency state in which human and mouse stem cells exist in vitro. Stem cells existing in the na ïve ground state express lower overall connexin levels but are still capable of gap junctional intercellular communication. As pluripotent stem cells become “primed” for differentiation, connexin expression (most notably Cx43) is significantly upregulated. Importantly, human and mouse stem cell s existing at both ends of the pluripotency continuum appear to retain their signature pluripotency profiles, even in the absence of Cx43. Abst...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Jessica L. Esseltine, Courtney R. Brooks, Nicole A. Edwards, Mathushan Subasri, Jacinda Sampson, Cheryle S éguin, Dean H. Betts, Dale W. Laird Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells: Concise review
Schematic representation of the key processes of lipid metabolism that could be targeted in CSCs and their associated metabolic regulators. AbstractEmerging evidences in cancer metabolomics have identified reprogrammed metabolic pathways to be a major hallmark of cancer, amongst which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Malini Visweswaran, Frank Arfuso, Sudha Warrier, Arun Dharmarajan Tags: Cancer Stem Cells Source Type: research

Unlocking the Paradoxical Endogenous Stem Cell Response after Spinal Cord Injury
Response of spinal cord ependymal stem cells to spinal cord injury. A, Glutamate stimulates neural stem/progenitor cell (NSPC) proliferation and enhances survival through AMPA receptor activation. B, M1 macrophages increase pro ‐inflammatory cytokine mRNA expression in NSPCs and enhance proliferation through MAPK‐Sox2 signaling. M2 macrophages increase anti‐inflammatory cytokine mRNA expression in NSPCs, reduce proliferation, and increase neuronal differentiation. C, Myelin‐derived inhibitory proteins limit NSPC pr oliferation and neuronal differentiation via NgR1 signaling. D, NSPCs maintain a high endogenous leve...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Laureen D. Hachem, Andrea J. Mothe, Charles H. Tator Tags: Tissue ‐Specific Stem Cells Source Type: research

Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells
The formin mDia2 is localized to the nucleus of the mesenchymal stem cell, while mDia1 is restricted to the cytoplasm. mDia2 is critical to function of the actin ‐lamin nucleoskeleton where it inhibits lineage commitment. When mDia2 is deficient, the lamin B1 nucleoskeleton is disrupted, activating osteogenesis, but not adipogenesis. AbstractNuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow derived MSCs, the principal diaphanous ‐related formin Diaph3 (mDia2) is present in the nucleus and regulates intranuclear actin polymerization, while Diaph1 (mDia1) is localized...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Jeyantt S. Sankaran, Buer Sen, Amel Dudakovic, Christopher R. Paradise, Tony Perdue, Zhihui Xie, Cody McGrath, Maya Styner, Joshua Newberg, Gunes Uzer, Andre J. Wijnen, Janet Rubin Tags: Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics Source Type: research

Proteasome Activation by Insulin ‐like Growth Factor‐1/Nuclear Factor Erythroid 2‐related Factor 2 Signaling Promotes Exercise‐induced Neurogenesis
This study shows that voluntary exercise causes hippocampal proteasome activation to improve adult neural progenitor cells activity. Mechanistically, exercise induces the increase of insulin like growth factor 1 (IGF ‐1) in serum and hippocampus, which in turn triggers the nuclear translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2) to promote the expression of the key proteasome subunit PSMB5 to enhance adult neurogenesis. This finding reveals novel insights into the modulation of adult neuro genesis through proteasome activation, which could be achieved by targeting the IGF‐1/Nrf2 signaling pathway. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Xiaojie Niu, Yunhe Zhao, Na Yang, Xuechun Zhao, Wei Zhang, Xiaowen Bai, Ang Li, Wulin Yang, Li Lu Tags: Tissue ‐Specific Stem Cells Source Type: research

Tunable hydrogels for mesenchymal stem cell delivery: integrin ‐induced transcriptome alterations and hydrogel optimization for human wound healing
PEG ‐8‐norbornene (PEG‐8‐Nb) and the peptide cross‐linker GCRDVPMS↓MRGGDRCG (that degrades in response to MMP ‐1, 2, 3, 7, and 9) were reacted, with the aid of the photoinitiator LAP, in the presence of MSC to form 3D hydrogel cultures. Parallel cultures were established similarly but with the addition of cysteine‐functionalized integrin‐binding small molecules, RGDS or LLP2A. MSC transcriptome profil ing revealed that hydrogel cultures altered the expression of genes important for extracellular matrix production, glycosylation, metabolism, and gene epigenetic regulation. AbstractTherapeutic applicatio...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Alina I. Marusina, Alexander A. Merleev, Jesus I. Luna, Laura Olney, Nathan E. Haigh, Daniel Yoon, Chen Guo, Elisa M. Ovadia, Michiko Shimoda, Guillaume Luxardi, Sucharita Boddu, Nelvish N. Lal, Yoshikazu Takada, Kit S. Lam, Ruiwu Liu, R. R Tags: Regenerative Medicine Source Type: research

Mesenchymal stem cells alleviate AQP ‐4‐dependent glymphatic dysfunction and improve brain distribution of antisense oligonucleotides in BACHD mice
In this study, the glymphatic system was found to be pivotal in ASO distribution. Moreover, an intravenously injection of MSCs (IV ‐MSC) rescued the loss of AQP‐4 in an HD mouse model. Since AQP‐4 is a critical channel in the brain glymphatic system, more ASOs were found in the brain tissue and a lower mutant HTT level was present in an HD mouse model with an IV‐MSC injection. In summary, IV‐MSC may be a potential the rapy to enhance ASO distribution efficiency and promote its therapeutic outcome in HD patients. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Teng ‐teng Wu, Feng‐juan Su, Yan‐qing Feng, Bin Liu, Ming‐yue Li, Feng‐yin Liang, Ge Li, Xue‐jiao Li, Yu Zhang, Zhong‐qiong Cai, Zhong Pei Tags: Regenerative Medicine Source Type: research

Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells
This study demonstrates that Canonical Wnt signaling promotes cardiac pacemaker lineage from Flk1+/PdgfR ‐α+ cardiac progenitors. Thede novo pacemaker cells exhibit hallmark features of native cardiac pacemaker cells, attesting to their therapeutic potential for cardiac rhythm ‐related diseases. (Source: Stem Cells)
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Wenbin Liang, Pengcheng Han, Elizabeth H. Kim, Jordan Mak, Rui Zhang, Angelo G. Torrente, Joshua I. Goldhaber, Eduardo Marb án, Hee Cheol Cho Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Dynamic regulation of connexins in stem cell pluripotency
Schematic model depicting expression levels of connexins relative to the pluripotency state in which human and mouse stem cells exist in vitro. Stem cells existing in the na ïve ground state express lower overall connexin levels but are still capable of gap junctional intercellular communication. As pluripotent stem cells become “primed” for differentiation, connexin expression (most notably Cx43) is significantly upregulated. Importantly, human and mouse stem cell s existing at both ends of the pluripotency continuum appear to retain their signature pluripotency profiles, even in the absence of Cx43. Abst...
Source: Stem Cells - October 24, 2019 Category: Stem Cells Authors: Jessica L. Esseltine, Courtney R. Brooks, Nicole A. Edwards, Mathushan Subasri, Jacinda Sampson, Cheryle S éguin, Dean H. Betts, Dale W. Laird Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

SPARC Promotes Self ‐Renewal of Limbal Epithelial Stem Cells and Ocular Surface Restoration through JNK and p38‐MAPK Signaling Pathways
Conclusion: SPARC promotes proliferation while suppressing spontaneous differentiation of LESCs through JNK and p38‐MAPK signaling pathways, suggesting that SPARC is a promising factor for the improvement of LESCs culture in vitro and in vivo.© AlphaMed Press 2019Significance StatementIn this study, we confirmed that secreted protein acidic and rich in cysteine (SPARC) in proper concentration promoted proliferation while suppressed spontaneous differentiation of limbal epithelial stem cells (LESCs) through JNK/p38 MAPK signal pathway in vitro. In corneal wound model, exogenous SPARC accelerated corneal epithelial wo...
Source: Stem Cells - October 23, 2019 Category: Stem Cells Authors: Jing Zhu, Le ‐yi Wang, Chong‐yun Li, Jia‐yin Wu, Yu‐ting Zhang, Kun‐peng Pang, Yan Wei, Li‐qun Du, Mei Liu, Xin‐yi Wu Tags: Tissue ‐Specific Stem Cells Source Type: research