Clinical and Molecular Consequences of Fusion Genes in Myeloid Malignancies
Schematic demonstrating the production and consequences of oncogenic fusion proteins produced by chromosomal rearragnements. AbstractLeukemias are heterogeneous diseases characterized by aberrant hematopoietic stem and progenitor cells (HSPCs). Oncogenic fusion genes and proteins, produced via gross chromosomal rearrangements such as chromosomal translocation, insertion, and inversion, play important roles in hematologic malignancies. These oncoproteins alter fundamental cellular properties such as self ‐renewal, differentiation, and proliferation, and confer leukemogenic potential to HSPCs. In addition to providing fund...
Source: Stem Cells - August 3, 2020 Category: Stem Cells Authors: Toshihiro Matsukawa, Peter D. Aplan Tags: Cancer Stem Cells Source Type: research

Accelerated Differentiation of Human Pluripotent Stem Cells into Neural Lineages via an Early Intermediate Ectoderm Population
This study describes that inhibiting selected signaling pathways enables the immediate exit from pluripotency and converts the stem cells within 24  hours into precursor cells that can be rapidly directed to generate desired neural populations desirable for research and potential cell therapies. This work removes a historical bottleneck that has prevented improving the control and speed of making neural cells from hPSCs and will likely change the way human neurons are generated in the future. (Source: Stem Cells)
Source: Stem Cells - August 3, 2020 Category: Stem Cells Authors: Patrick Walsh, Vincent Truong, Sushmita Nayak, Marietta Sald ías Montivero, Walter C. Low, Ann M. Parr, James R. Dutton Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

A Preview of Selected Articles
STEM CELLS, Volume 38, Issue 8, Page 917-920, August 2020. (Source: Stem Cells)
Source: Stem Cells - July 28, 2020 Category: Stem Cells Authors: Stuart P. Atkinson Tags: PREVIEWS Source Type: research

Cover Image
Implantation of the clinical ‐grade human neural stem cell line, CTX0E03, can survive and differentiate into striatal neurons in the quinolinic acid‐lesioned rodent model of Huntington's disease. Figure shows the widespread distribution of survived CTX cells that were differentiated into GAD65/67‐positive GABAergic neuron s 13 weeks after transplantation.See Yoon et al. beginning on page936. (Source: Stem Cells)
Source: Stem Cells - July 28, 2020 Category: Stem Cells Tags: COVER IMAGE Source Type: research

Issue Information
STEM CELLS, Volume 38, Issue 8, Page i-viii, August 2020. (Source: Stem Cells)
Source: Stem Cells - July 28, 2020 Category: Stem Cells Tags: ISSUE INFORMATION Source Type: research

DNMT3B deficiency alters mitochondrial biogenesis and α‐ketoglutarate levels in human embryonic stem cells
Human embryonic stem cells deficient for DNMT3B exhibit increased expression of isocitrate dehydrogenases and buildup of α‐ketoglutarate. In addition, loss of DNMT3B disrupts the cells mitochondrial fusion and fission balance, reduces mitochondrial DNA levels, and elicits a switch from glycolysis to oxidative phosphorylation. AbstractEmbryonic stem cell (ESC) renewal and differentiation is regulated by metabolites that serve as co ‐factors for epigenetic enzymes. Increase of α‐ketoglutarate (α‐KG), a co‐factor for histone and DNA demethylases, triggers multi‐lineage differentiation in human ES...
Source: Stem Cells - July 11, 2020 Category: Stem Cells Authors: Artur Cieslar ‐Pobuda, Theresa D. Ahrens, Safak Caglayan, Sidney Behringer, Luciana Hannibal, Judith Staerk Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

MMP13 and TIMP1 are functional markers for two different potential modes of action by mesenchymal stem/stromal cells when treating osteoarthritis
Ageing of human Mesenchymal stem/stromal cells (MSCs)in vitro through prolonged culture and passage results in loss of their chondrogenic potential but no reduction in their trophic repair capacity, allowing the identification of gene and protein markers of these different functions. AbstractMesenchymal stem cells (MSCs) have been investigated as a potential injectable therapy for the treatment of knee osteoarthritis, with some evidence of success in preliminary human trials. However, optimisation and scale ‐up of this therapeutic approach depends on the identification of functional markers that are linked to their mecha...
Source: Stem Cells - July 11, 2020 Category: Stem Cells Authors: Anna Salerno, Kyla Brady, Margot Rikkers, Chao Li, Eva Caama ño‐Gutierrez, Francesco Falciani, Ashley W. Blom, Michael R. Whitehouse, Anthony P. Hollander Tags: Regenerative Medicine Source Type: research

DNMT3B deficiency alters mitochondrial biogenesis and α‐ketoglutarate levels in human embryonic stem cells
Human embryonic stem cells deficient for DNMT3B exhibit increased expression of isocitrate dehydrogenases and buildup of α‐ketoglutarate. In addition, loss of DNMT3B disrupts the cells mitochondrial fusion and fission balance, reduces mitochondrial DNA levels, and elicits a switch from glycolysis to oxidative phosphorylation. AbstractEmbryonic stem cell (ESC) renewal and differentiation is regulated by metabolites that serve as co ‐factors for epigenetic enzymes. Increase of α‐ketoglutarate (α‐KG), a co‐factor for histone and DNA demethylases, triggers multi‐lineage differentiation in human ES...
Source: Stem Cells - July 11, 2020 Category: Stem Cells Authors: Artur Cieslar ‐Pobuda, Theresa D. Ahrens, Safak Caglayan, Sidney Behringer, Luciana Hannibal, Judith Staerk Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

MMP13 and TIMP1 are functional markers for two different potential modes of action by mesenchymal stem/stromal cells when treating osteoarthritis
Ageing of human Mesenchymal stem/stromal cells (MSCs)in vitro through prolonged culture and passage results in loss of their chondrogenic potential but no reduction in their trophic repair capacity, allowing the identification of gene and protein markers of these different functions. AbstractMesenchymal stem cells (MSCs) have been investigated as a potential injectable therapy for the treatment of knee osteoarthritis, with some evidence of success in preliminary human trials. However, optimisation and scale ‐up of this therapeutic approach depends on the identification of functional markers that are linked to their mecha...
Source: Stem Cells - July 11, 2020 Category: Stem Cells Authors: Anna Salerno, Kyla Brady, Margot Rikkers, Chao Li, Eva Caama ño‐Gutierrez, Francesco Falciani, Ashley W. Blom, Michael R. Whitehouse, Anthony P. Hollander Tags: Regenerative Medicine Source Type: research

Generation of cerebral cortical GABAergic interneurons from pluripotent stem cells
Cortical interneurons are inhibitory GABAergic neurons that originate in the caudal or medial ganglionic eminences (MGE) of the embryonic subcortical telencephalon, then migrate into the cortex. Differentiation conditions mimicking developmental signals found in the telencephalon are used to generate interneurons from embryonic and induced pluripotent stem cells. Stem cell derived interneurons should be validated by migratory capacity, morphology, gene and protein expression, and electrophysiology. AbstractThe cerebral cortex functions by the complex interactions of intrinsic and extrinsic neuronal activities, glial action...
Source: Stem Cells - July 7, 2020 Category: Stem Cells Authors: Megan Fitzgerald, Nathaniel Sotuyo, David J. Tischfield, Stewart A. Anderson Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Alternative splicing in mesenchymal stem cell differentiation
Mesenchymal stem cells (MSCs) are essential cell sources for bone, fat tissues, cartilage, and other connective tissues inside the body and in the test tube. Alternative splicing (AS) of pre ‐mRNAs, which encode critical determinants of MSC differentiation, regulates the MSC differentiation by specifying cell type‐specific transcriptome or antagonizing the function of the WT protein. AbstractThe differentiation and maturation of mesenchymal stem cells (MSCs) to mesodermal and other lineages are known to be controlled by various extrinsic and intrinsic signals. The dysregulation of the MSC differentiation balance has be...
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Jung Woo Park, Siyi Fu, Borong Huang, Ren ‐He Xu Tags: Tissue ‐Specific Stem Cells Source Type: research

Allogeneic adipose ‐derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF‐1α/IL‐10 pathway
This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capac ity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages towards the anti‐inflammatory M2 phenotype. We further demonstrated that ASCs‐derived interleukin 10 (IL‐10), mediated by hypoxia inducible factor‐1α (HIF‐1α), played a crucial role in the induction of M2 macroph...
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Junchao Liu, Peng Qiu, Jinbao Qin, Xiaoyu Wu, Xin Wang, Xinrui Yang, Bo Li, Wenjie Zhang, Kaichuang Ye, Zhiyou Peng, Xinwu Lu Tags: Regenerative Medicine Source Type: research

The Sca ‐1+ and Sca‐1− mouse prostatic luminal cell lineages are independently sustained
This study corroborates the heterogeneity of the mouse prostate luminal cell lineage and show that the adult mouse prostate luminal cell lineage is maintained by distinct cellular entities rather than a single progenitor population.© AlphaMed Press 2020Significance StatementThis study characterizes the phenotypic and functional heterogeneity of the mouse prostate luminal epithelial cells and demonstrates a critical role of Sox2 in maintaining the facultative bipotent differentiation capacity of the Sca ‐1+ luminal cells. (Source: Stem Cells)
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Oh ‐Joon Kwon, Jong Min Choi, Li Zhang, Deyong Jia, Zhouyihan Li, Yiqun Zhang, Sung Yun Jung, Chad J. Creighton, Li Xin Tags: Tissue ‐Specific Stem Cells Source Type: research

Alternative splicing in mesenchymal stem cell differentiation
Mesenchymal stem cells (MSCs) are essential cell sources for bone, fat tissues, cartilage, and other connective tissues inside the body and in the test tube. Alternative splicing (AS) of pre ‐mRNAs, which encode critical determinants of MSC differentiation, regulates the MSC differentiation by specifying cell type‐specific transcriptome or antagonizing the function of the WT protein. AbstractThe differentiation and maturation of mesenchymal stem cells (MSCs) to mesodermal and other lineages are known to be controlled by various extrinsic and intrinsic signals. The dysregulation of the MSC differentiation balance has be...
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Jung Woo Park, Siyi Fu, Borong Huang, Ren ‐He Xu Tags: Tissue ‐Specific Stem Cells Source Type: research

Allogeneic adipose ‐derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF‐1α/IL‐10 pathway
This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capac ity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages towards the anti‐inflammatory M2 phenotype. We further demonstrated that ASCs‐derived interleukin 10 (IL‐10), mediated by hypoxia inducible factor‐1α (HIF‐1α), played a crucial role in the induction of M2 macroph...
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Junchao Liu, Peng Qiu, Jinbao Qin, Xiaoyu Wu, Xin Wang, Xinrui Yang, Bo Li, Wenjie Zhang, Kaichuang Ye, Zhiyou Peng, Xinwu Lu Tags: Regenerative Medicine Source Type: research

The Sca ‐1+ and Sca‐1− mouse prostatic luminal cell lineages are independently sustained
This study corroborates the heterogeneity of the mouse prostate luminal cell lineage and show that the adult mouse prostate luminal cell lineage is maintained by distinct cellular entities rather than a single progenitor population.© AlphaMed Press 2020Significance StatementThis study characterizes the phenotypic and functional heterogeneity of the mouse prostate luminal epithelial cells and demonstrates a critical role of Sox2 in maintaining the facultative bipotent differentiation capacity of the Sca ‐1+ luminal cells. (Source: Stem Cells)
Source: Stem Cells - July 6, 2020 Category: Stem Cells Authors: Oh ‐Joon Kwon, Jong Min Choi, Li Zhang, Deyong Jia, Zhouyihan Li, Yiqun Zhang, Sung Yun Jung, Chad J. Creighton, Li Xin Tags: Tissue ‐Specific Stem Cells Source Type: research

Regulation of ABO blood group antigen expression by miR ‐331‐3p and miR‐1908‐5p during hematopoietic stem cell differentiation
miRNAs were identified as important regulators of ABH antigen expression. miR ‐331‐3p and miR‐1908‐5p directly target glycosyltransferase A and B mRNA. The simultaneous targeting of the TF SP1 by miR‐331‐3p further enhances this effect, rendering SP1 incapable of binding to the ABO gene promoter, resulting in downregulation of blood group A antigen expression. AbstractThe ABO blood group system is the most important factor in clinical transfusion medicine and is implicated in a number of human diseases. ABO antigens are not confined to red blood cells (RBCs) and are widely expressed in a variety of human cells ...
Source: Stem Cells - July 4, 2020 Category: Stem Cells Authors: Romy Kronstein ‐Wiedemann, Paulina Nowakowska, Peter Milanov, Knut Gubbe, Erhard Seifried, Peter Bugert, Triantafyllos Chavakis, Torsten Tonn Tags: Translational And Clinical Research Source Type: research

Epithelial cadherin regulates transition between the na ïve and primed pluripotent states in mouse embryonic stem cells
This study highlights a phenomena found in both primed pluripotent state and cancer stemness and links it to loss of E‐cad. Data are available via ProteomeXchange with identifier PXD012679. (Source: Stem Cells)
Source: Stem Cells - July 4, 2020 Category: Stem Cells Authors: Aseel M. Sharaireh, Lorna M. Fitzpatrick, Chris M. Ward, Tristan R. McKay, Richard D. Unwin Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Regulation of ABO blood group antigen expression by miR ‐331‐3p and miR‐1908‐5p during hematopoietic stem cell differentiation
miRNAs were identified as important regulators of ABH antigen expression. miR ‐331‐3p and miR‐1908‐5p directly target glycosyltransferase A and B mRNA. The simultaneous targeting of the TF SP1 by miR‐331‐3p further enhances this effect, rendering SP1 incapable of binding to the ABO gene promoter, resulting in downregulation of blood group A antigen expression. AbstractThe ABO blood group system is the most important factor in clinical transfusion medicine and is implicated in a number of human diseases. ABO antigens are not confined to red blood cells (RBCs) and are widely expressed in a variety of human cells ...
Source: Stem Cells - July 4, 2020 Category: Stem Cells Authors: Romy Kronstein ‐Wiedemann, Paulina Nowakowska, Peter Milanov, Knut Gubbe, Erhard Seifried, Peter Bugert, Triantafyllos Chavakis, Torsten Tonn Tags: Translational And Clinical Research Source Type: research

Epithelial cadherin regulates transition between the na ïve and primed pluripotent states in mouse embryonic stem cells
This study highlights a phenomena found in both primed pluripotent state and cancer stemness and links it to loss of E‐cad. Data are available via ProteomeXchange with identifier PXD012679. (Source: Stem Cells)
Source: Stem Cells - July 4, 2020 Category: Stem Cells Authors: Aseel M. Sharaireh, Lorna M. Fitzpatrick, Chris M. Ward, Tristan R. McKay, Richard D. Unwin Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Platform to study intracellular polystyrene nanoplastic pollution and clinical outcomes
Schematic illustration of the platform and experimental design with 40  nm polystyrene nanoplastics. Human blastocysts and human induced pluripotent stem cells were exposed for 24 hours to polystyrene nanoitems and used for whole transcriptome sequencing and in depth RNA analysis through Next‐Generation Sequencing technology. In preprocessment, gene IDs were tran slated, scaled, normalized, and used for signaling pathways, analysis, and delivery of the report. AbstractIncreased pollution by plastics has become a serious global environmental problem, but the concerns for human health have been raised after r...
Source: Stem Cells - July 2, 2020 Category: Stem Cells Authors: Sanja Bojic, Matias M. Falco, Petra Stojkovic, Biljana Ljujic, Marina Gazdic Jankovic, Lyle Armstrong, Nebojsa Markovic, Joaquin Dopazo, Majlinda Lako, Roman Bauer, Miodrag Stojkovic Tags: Stem Cell Technology: Epigenetics, Genomics, Proteomics, And Metabonomics Source Type: research

Cover Image
A representative micrograph of an inner ear progenitor cell ‐derived spheroid. Immunofluorescence analysis shows that RhoA was mainly located in the nucleus (green); F‐actin labeled the cytoskeleton (red) and DAPI labeled the nucleus (blue). Accumulated RhoA and intensive F‐actin cytoskeleton polymerization were found at the edges of the spheroid.See Xia et al. beginning on page860. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Tags: COVER IMAGE Source Type: research

Issue Information
STEM CELLS, Volume 38, Issue 7, Page i-viii, July 2020. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Tags: ISSUE INFORMATION Source Type: research

A preview of selected articles
STEM CELLS, Volume 38, Issue 7, Page 815-817, July 2020. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Authors: Stuart P. Atkinson Tags: PREVIEWS Source Type: research

Cover Image
A representative micrograph of an inner ear progenitor cell ‐derived spheroid. Immunofluorescence analysis shows that RhoA was mainly located in the nucleus (green); F‐actin labeled the cytoskeleton (red) and DAPI labeled the nucleus (blue). Accumulated RhoA and intensive F‐actin cytoskeleton polymerization were found at the edges of the spheroid.See Xia et al. beginning on page860. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Tags: COVER IMAGE Source Type: research

Issue Information
STEM CELLS, Volume 38, Issue 7, Page i-viii, July 2020. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Tags: ISSUE INFORMATION Source Type: research

A preview of selected articles
STEM CELLS, Volume 38, Issue 7, Page 815-817, July 2020. (Source: Stem Cells)
Source: Stem Cells - June 30, 2020 Category: Stem Cells Authors: Stuart P. Atkinson Tags: PREVIEWS Source Type: research

The epitranscriptome landscape of small noncoding RNAs in stem cells
The multifunctional roles RNA post ‐transcriptional modifications, the epitranscriptome, could play to regulate stem cell biology. Stem cells coordinate epitranscriptome responses by expressing particular combinations of readers, writers, and erasers, which deposit, process, and remove transcriptome modifications. It is through the se orchestrates mechanisms that the epitranscriptome modulate transcriptomes and proteomes to fine‐tune stem cell fate decisions. AbstractStem cells (SCs) are unique cells that have an inherent ability to self ‐renew or differentiate. Both fate decisions are strongly regulated at the molec...
Source: Stem Cells - June 29, 2020 Category: Stem Cells Authors: James M. W. R. McElhinney, Ayesha Hasan, Abdulrahim A. Sajini Tags: Stem Cell Technology: Epigenetics, Genomics, Proteomics, And Metabonomics Source Type: research

Canonical Notch signaling is required for bone morphogenetic protein ‐mediated human osteoblast differentiation
Bone morphogenetic protein (BMP) stimulation of bone ‐marrow‐derived human mesenchymal progenitor cells (hMSCs) increases Notch proteins via increased Notch ligand Jagged1 expression. Canonical Notch signaling is required for BMP‐induced ALPL expression and osteoblastic commitment of hMSCs. Both BMP‐induced osteoblastogenesis and Notch‐induc ed osteoblastogenesis require Runx2. AbstractOsteoblast differentiation of bone ‐marrow‐derived human mesenchymal stem cells (hMSC) can be induced by stimulation with canonical Notch ligand, Jagged1, or bone morphogenetic proteins (BMPs). However, it remains elusive how t...
Source: Stem Cells - June 24, 2020 Category: Stem Cells Authors: Yadav Wagley, Alessandra Chesi, Parker K. Acevedo, Sumei Lu, Andrew D. Wells, Matthew E. Johnson, Struan F. A. Grant, Kurt D. Hankenson Tags: Tissue ‐Specific Stem Cells Source Type: research

Mapping developmental trajectories and subtype diversity of normal and glaucomatous human retinal ganglion cells by single ‐cell transcriptome analysis
Single ‐cell transcriptome‐based developmental trajectories reveal developmental abnormalities in glaucoma patient‐specific retinal ganglion cells (RGCs). A comparison of the developmental trajectories, based on lineage‐ and stage‐specific transcriptional signature of differentiating glaucoma pat ient (SIX6risk allele) ‐specific and control induced pluripotent stem cells along the RGC lineage, revealed that theSIX6risk allele RGCs are compromised in mature phenotype and subtype composition, including those that are degeneration ‐resistant vs controls. AbstractGlaucoma is characterized by a progressive degener...
Source: Stem Cells - June 18, 2020 Category: Stem Cells Authors: Pooja Teotia, Meng Niu, Iqbal Ahmad Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Wnt/ β‐catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema
Wnt/ β‐catenin signaling supports alveolar, bronchiolar, and bronchioalveolar organoids formation from distal lung epithelial progenitors of healthy lungs. In emphysema, a chronic lung disease characterized by distal tissue destruction and reduction of Wnt/β‐catenin activity, distal lung epithelial progenitors are impaired and form fewer alveolar organoids. Activation of Wnt/β‐catenin signaling rescues alveolar organoid formation, thus revealing a novel mechanism of lung epithelial progenitor cell activation in emphysema. AbstractWnt/ β‐catenin signaling regulates progenitor cell fate decisions ...
Source: Stem Cells - June 18, 2020 Category: Stem Cells Authors: Yan Hu, John ‐Poul Ng‐Blichfeldt, Chiharu Ota, Chiara Ciminieri, Wenhua Ren, Pieter S. Hiemstra, Jan Stolk, Reinoud Gosens, Melanie Königshoff Tags: Tissue ‐Specific Stem Cells Source Type: research

Mapping developmental trajectories and subtype diversity of normal and glaucomatous human retinal ganglion cells by single ‐cell transcriptome analysis
Single ‐cell transcriptome‐based developmental trajectories reveal developmental abnormalities in glaucoma patient‐specific retinal ganglion cells (RGCs). A comparison of the developmental trajectories, based on lineage‐ and stage‐specific transcriptional signature of differentiating glaucoma pat ient (SIX6risk allele) ‐specific and control induced pluripotent stem cells along the RGC lineage, revealed that theSIX6risk allele RGCs are compromised in mature phenotype and subtype composition, including those that are degeneration ‐resistant vs controls. AbstractGlaucoma is characterized by a progressive degener...
Source: Stem Cells - June 18, 2020 Category: Stem Cells Authors: Pooja Teotia, Meng Niu, Iqbal Ahmad Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Advancing physiological maturation in human induced pluripotent stem cell ‐derived cardiac muscle by gene editing an inducible adult troponin isoform switch
hiPSC ‐CMs are gene edited to contain an inducible cardiac troponin I (cTnI) expression cassette. When these cells are treated with doxycycline, they express cTnI. Expression of cTnI is sufficient to promote a phenotype with physiologic markers of mature myocytes, including faster relaxation and improve d adrenergic responsivity, compared to nonedited cells which only express slow skeletal troponin I. AbstractAdvancing maturation of stem cell ‐derived cardiac muscle represents a major barrier to progress in cardiac regenerative medicine. Cardiac muscle maturation involves a myriad of gene, protein, and cell‐based tra...
Source: Stem Cells - June 16, 2020 Category: Stem Cells Authors: Matthew Wheelwright, Jennifer Mikkila, Fikru B. Bedada, Mohammad A. Mandegar, Brian R. Thompson, Joseph M. Metzger Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Enhanced Collection of Phenotypic and Engrafting Human Cord Blood Hematopoietic Stem Cells at 4 °C
AbstractHematopoietic stem cell (HSC) numbers collected in cord blood (CB) at the birth of a baby is a limiting factor for efficacious use of CB in hematopoietic cell transplantation (HCT). We now demonstrate that collecting and processing of human CB at 4 °C within minutes of the baby's birth results in significantly enhanced numbers of rigorously defined phenotypic HSC and self‐renewing NSG immune‐deficient mouse engrafting and SCID‐repopulating cells. This was associated with decreased numbers of hematopoietic progenitor cells (HPC), as note d previously for hypoxia collected/processed cells blocking ambient a...
Source: Stem Cells - June 14, 2020 Category: Stem Cells Authors: Hal E. Broxmeyer, Scott Cooper, Maegan L. Capitano Tags: Tissue ‐Specific Stem Cells Source Type: research

Canonical Notch Signaling is Required for Bone Morphogenetic Protein ‐mediated Human Osteoblast Differentiation
BMP stimulation of bone ‐marrow derived human mesenchymal progenitor cells (hMSCs) increases Notch proteins via increased Notch ligand Jagged1 expression. Canonical Notch signaling is required for BMPinduced ALPL expression and osteoblastic commitment of hMSCs. Both BMP‐induced osteoblastogenesis and Notch‐induced os teoblastogenesis require Runx2. AbstractOsteoblast differentiation of bone ‐marrow derived human mesenchymal stem cells (hMSC) can be induced by stimulation with either canonical Notch ligand, Jagged1, or bone morphogenetic proteins (BMP). However, it remains elusive how these two pathways lead to the ...
Source: Stem Cells - June 14, 2020 Category: Stem Cells Authors: Yadav Wagley, Alessandra Chesi, Parker K. Acevedo, Sumei Lu, Andrew D. Wells, Matthew E. Johnson, Struan F. A. Grant, Kurt D. Hankenson Tags: Tissue ‐Specific Stem Cells Source Type: research

Enhanced Collection of Phenotypic and Engrafting Human Cord Blood Hematopoietic Stem Cells at 4 °C
AbstractHematopoietic stem cell (HSC) numbers collected in cord blood (CB) at the birth of a baby is a limiting factor for efficacious use of CB in hematopoietic cell transplantation (HCT). We now demonstrate that collecting and processing of human CB at 4 °C within minutes of the baby's birth results in significantly enhanced numbers of rigorously defined phenotypic HSC and self‐renewing NSG immune‐deficient mouse engrafting and SCID‐repopulating cells. This was associated with decreased numbers of hematopoietic progenitor cells (HPC), as note d previously for hypoxia collected/processed cells blocking ambient a...
Source: Stem Cells - June 14, 2020 Category: Stem Cells Authors: Hal E. Broxmeyer, Scott Cooper, Maegan L. Capitano Tags: Tissue ‐Specific Stem Cells Source Type: research

Stem Cell Homing: From Physiology to Therapeutics
Steps in hematopoietic stem cell (HSC) homing and egress to and from marrow. Homing (left hand panel) occurs in the marrow sinusoidal endothelium. (1) Selectin ‐mediated braking or rolling occurs. Selectins involved include P‐selectin which interacts with CD162, SLex, and E‐selectin which recognizes CD15, SLex, and CD162 on stem cells. (2) HSCs migrate on adhesion ligands presented by the vascular endothelium, so‐called tethering. This involves CD4 9d‐f, CD11b, and CD11c on the hematopoietic stem and progenitor cells and CD106/fibronectin, laminin, and ICAM‐1 on endothelium as well as numerous other adhesion re...
Source: Stem Cells - June 11, 2020 Category: Stem Cells Authors: Jane L. Liesveld, Naman Sharma, Omar S. Aljitawi Tags: Translational and Clinical Research Source Type: research

Wnt/ β‐catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema
Wnt/ β‐catenin signaling supports alveolar, bronchiolar and bronchioalveolar organoids formation from distal lung epithelial progenitors of healthy lungs. In emphysema, a chronic lung disease characterized by distal tissue destruction and reduction of Wnt/β‐catenin activity, distal lung epithelial progenitors are impaired and form fewer alveolar organoids. Activation of Wnt/β‐catenin signaling rescues alveolar organoid formation, thus revealing a novel mechanism of lung epithelial progenitor cell activation in emphysema. AbstractWnt/ β‐catenin signaling regulates progenitor cell fate decisions d...
Source: Stem Cells - June 11, 2020 Category: Stem Cells Authors: Yan Hu, John ‐Poul Ng‐Blichfeldt, Chiharu Ota, Chiara Ciminieri, Wenhua Ren, Pieter S. Hiemstra, Jan Stolk, Reinoud Gosens, Melanie Königshoff Tags: Tissue ‐Specific Stem Cells Source Type: research

Replicates in stem cell models —How complicated!
Current complexities in human pluripotent stem cell (hPSC) ‐based studies. hPSC studies begin with the recruitment of patients harboring disease‐associated gene variant(s) that may increase susceptibility to disease development. Somatic reprogramming is then performed to derive patient‐specific human induced pluripotent stem cells (hiPSCs), followed b y step‐wise directed differentiation to a relevant cell type before qualitative/quantitative assays are performed to assess for phenotypic or gene expression differences between the healthy and diseased hiPSCs. (Source: Stem Cells)
Source: Stem Cells - June 10, 2020 Category: Stem Cells Authors: Jun ‐Wei Chan, Adrian K. K. Teo Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

Lineage ‐specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1‐RUNX2 association in neural crest‐derived osteoprogenitors
Human pluripotent stem cells were stepwise differentiated toward paraxial mesoderm ‐, lateral plate mesoderm‐, and neural crest‐derived osteogenic progenitors (OPs). Transcriptomic signatures of these three cell subpopulations were identified, with a new finding of high FGF1 levels and its association with RUNX2 in neural crest‐derived OPs. AbstractHuman pluripotent stem cells (hPSCs) can provide a platform to model bone organogenesis and disease. To reflect the developmental process of the human skeleton, hPSC differentiation methods should include osteogenic progenitors (OPs) arising from three distinct embryonic...
Source: Stem Cells - June 9, 2020 Category: Stem Cells Authors: Fahad Kidwai, Byron W. H. Mui, Deepika Arora, Kulsum Iqbal, Madison Hockaday, Luis Fernandez Castro Diaz, Natasha Cherman, Daniel Martin, Vamsee D. Myneni, Moaz Ahmad, Katarzyna Futrega, Sania Ali, Randall K. Merling, Dan S. Kaufman, Janice Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

A genomic biomarker that identifies human bone marrow ‐derived mesenchymal stem cells with high scalability
GSTT1 is a novel genomic biomarker of human mesenchymal stem cell (hMSC) scalability.GSTT1‐null (GSTT1*0/*0) hMSCs possess higher clonogenicity and proliferative capacity in comparison to homozygous positive (GSTT1*1/*1) cells. AbstractAlthough the application of human mesenchymal stem cells (hMSCs) to repair damaged or diseased tissues has proven relatively effective, both the donor ‐to‐donor variability in ex vivo expansion rates and the maintenance of stemness remain a bottleneck to widespread translation. Previous work from this laboratory stratified donors into those yielding hMSCs with high‐ or low‐growth c...
Source: Stem Cells - June 8, 2020 Category: Stem Cells Authors: Padmapriya Sathiyanathan, Rebekah M. Samsonraj, Clarissa L. L. Tan, Ling Ling, Alexander Lezhava, Victor Nurcombe, Lawrence W. Stanton, Simon M. Cool Tags: Regenerative Medicine Source Type: research

Galectin ‐3 diminishes Wnt signaling in the postnatal subventricular zone
Decreased Galectin ‐3 (Gal‐3) expression, by knockdown, increased Wnt/β‐catenin signaling whereas Gal‐3 overexpression decreased Wnt/β‐catenin signaling. We showed that Gal‐3 binds to β‐catenin. Concurrently, we found that Gal‐3 overexpression decreased proliferation and increased cell cycle exit. AbstractPostnatal subventricular zone (pSVZ) stem and progenitor cell proliferation is regulated by several developmental signaling pathways such as Wnt/ β‐catenin. However, the molecular regulation of Wnt function in the pSVZ is poorly understood. We previously showed that Wnt signaling is u...
Source: Stem Cells - June 8, 2020 Category: Stem Cells Authors: Osama Al ‐Dalahmah, James Nicholson, Swip Draijer, Luana Campos Soares, Francis G. Szele Tags: Tissue ‐Specific Stem Cells Source Type: research

A genomic biomarker that identifies human bone marrow ‐derived mesenchymal stem cells with high scalability
GSTT1 is a novel genomic biomarker of human mesenchymal stem cell (hMSC) scalability.GSTT1‐null (GSTT1*0/*0) hMSCs possess higher clonogenicity and proliferative capacity in comparison to homozygous positive (GSTT1*1/*1) cells. AbstractAlthough the application of human mesenchymal stem cells (hMSCs) to repair damaged or diseased tissues has proven relatively effective, both the donor ‐to‐donor variability in ex vivo expansion rates and the maintenance of stemness remain a bottleneck to widespread translation. Previous work from this laboratory stratified donors into those yielding hMSCs with high‐ or low‐growth c...
Source: Stem Cells - June 8, 2020 Category: Stem Cells Authors: Padmapriya Sathiyanathan, Rebekah M. Samsonraj, Clarissa L. L. Tan, Ling Ling, Alexander Lezhava, Victor Nurcombe, Lawrence W. Stanton, Simon M. Cool Tags: Regenerative Medicine Source Type: research

Pluripotent stem cell ‐derived retinal organoids for disease modeling and development of therapies
Retinal organoids offer a unique human model system to study mechanisms of disease pathogenesis and for developing therapies. AbstractRetinal diseases constitute a genetically and phenotypically diverse group of clinical conditions leading to vision impairment or blindness with limited treatment options. Advances in reprogramming of somatic cells to induced pluripotent stem cells and generation of three ‐dimensional organoids resembling the native retina offer promising tools to interrogate disease mechanisms and evaluate potential therapies for currently incurable retinal neurodegeneration. Next‐generation sequencing,...
Source: Stem Cells - June 7, 2020 Category: Stem Cells Authors: Kamil Kruczek, Anand Swaroop Tags: Regenerative Medicine Source Type: research