Log in to search using one of your social media accounts:

 

Retraction Notice to: In  Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling
Publication date: 13 February 2018 Source:Stem Cell Reports, Volume 10, Issue 2 Author(s): Kohei Yamamizu, Mio Iwasaki, Hitomi Takakubo, Takumi Sakamoto, Takeshi Ikuno, Mami Miyoshi, Takayuki Kondo, Yoichi Nakao, Masato Nakagawa, Haruhisa Inoue, Jun K. Yamashita (Source: Stem Cell Reports)
Source: Stem Cell Reports - February 14, 2018 Category: Stem Cells Source Type: research

Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance
Publication date: 13 February 2018 Source:Stem Cell Reports, Volume 10, Issue 2 Author(s): Nur Zafirah Zaidan, Kolin J. Walker, Jaime E. Brown, Leah V. Schaffer, Mark Scalf, Michael R. Shortreed, Gopal Iyer, Lloyd M. Smith, Rupa Sridharan The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongati...
Source: Stem Cell Reports - February 14, 2018 Category: Stem Cells Source Type: research

Triple S-Phase Labeling of Dividing Stem Cells
Publication date: 13 February 2018 Source:Stem Cell Reports, Volume 10, Issue 2 Author(s): Oleg Podgorny, Natalia Peunova, June-Hee Park, Grigori Enikolopov Marking replicating DNA with multiple labels presents the possibility of revealing new features and mechanisms of DNA synthesis and cell division; however, progression beyond double labeling has been hampered by cross-reactivity of label detection and scarcity of appropriate labels. Here, we present a method for triple S-phase labeling of the dividing cells, with a fourth label used to mark cells actively engaged in cell-cycle progression (e.g., using Ki67) or to...
Source: Stem Cell Reports - February 14, 2018 Category: Stem Cells Source Type: research

Ihor Lemischka (1953-2017)
Publication date: 13 February 2018 Source:Stem Cell Reports, Volume 10, Issue 2 Author(s): Peter Lansdorp (Source: Stem Cell Reports)
Source: Stem Cell Reports - February 14, 2018 Category: Stem Cells Source Type: research

Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction
In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis. Teaser In this article, Wu and colleagues demonstrate the therapeutic similarities of non-human primate iPSC-CMs and human iPSC-CMs to treat myocardial infarction by improving cardiac function and attenuating myocardial remodeling in a rodent myocardial infarction model. Mechanisms of iPSC-CM therapy include promotion of cell survival, angiogenesis, and inhibition of hypertrophy and f...
Source: Stem Cell Reports - February 2, 2018 Category: Stem Cells Source Type: research

Testicular Architecture Is Critical for Mediation of Retinoic Acid Responsiveness by Undifferentiated Spermatogonial Subtypes in the Mouse
Publication date: Available online 1 February 2018 Source:Stem Cell Reports Author(s): Tessa Lord, Melissa J. Oatley, Jon M. Oatley Spermatogenesis requires retinoic acid (RA) induction of the undifferentiated to differentiating transition in transit amplifying (TA) progenitor spermatogonia, whereas continuity of the spermatogenic lineage relies on the RA response being suppressed in spermatogonial stem cells (SSCs). Here, we discovered that, in mouse testes, both spermatogonial populations possess intrinsic RA-response machinery and exhibit hallmarks of the differentiating transition following direct exposure to RA, incl...
Source: Stem Cell Reports - February 2, 2018 Category: Stem Cells Source Type: research

In  Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells
In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs) into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs). These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRα1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients wi...
Source: Stem Cell Reports - February 2, 2018 Category: Stem Cells Source Type: research

Argonaute 2 Is Required for Extra-embryonic Endoderm Differentiation of Mouse Embryonic Stem Cells
Publication date: Available online 26 January 2018 Source:Stem Cell Reports Author(s): Richard Patryk Ngondo, Daniel Cirera-Salinas, Jian Yu, Harry Wischnewski, Maxime Bodak, Sandrine Vandormael-Pournin, Anna Geiselmann, Rahel Wettstein, Janina Luitz, Michel Cohen-Tannoudji, Constance Ciaudo In mouse, although four Argonaute (AGO) proteins with partly overlapping functions in small-RNA pathways exist, only Ago2 deficiency causes embryonic lethality. To investigate the role of AGO2 during mouse early development, we generated Ago2-deficient mouse embryonic stem cells (mESCs) and performed a detailed characterization of the...
Source: Stem Cell Reports - January 27, 2018 Category: Stem Cells Source Type: research

Reduced Self-Diploidization and Improved Survival of Semi-cloned Mice Produced from Androgenetic Haploid Embryonic Stem Cells through Overexpression of Dnmt3b
Publication date: Available online 27 January 2018 Source:Stem Cell Reports Author(s): Wenteng He, Xiaobai Zhang, Yalin Zhang, Weisheng Zheng, Zeyu Xiong, Xinjie Hu, Mingzhu Wang, Linfeng Zhang, Kun Zhao, Zhibin Qiao, Weiyi Lai, Cong Lv, Xiaochen Kou, Yanhong Zhao, Jiqing Yin, Wenqiang Liu, Yonghua Jiang, Mo Chen, Ruimin Xu, Rongrong Le, Chong Li, Hong Wang, Xiaoping Wan, Hailin Wang, Zhiming Han, Cizhong Jiang, Shaorong Gao, Jiayu Chen Androgenetic haploid embryonic stem cells (AG-haESCs) hold great promise for exploring gene functions and generating gene-edited semi-cloned (SC) mice. However, the high incidence of self-...
Source: Stem Cell Reports - January 27, 2018 Category: Stem Cells Source Type: research

Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC
Publication date: Available online 27 January 2018 Source:Stem Cell Reports Author(s): Fang Du, Qing Yu, Allen Chen, Doris Chen, Shirley ShiDu Yan Astrocytes, the most populous glial cell type in the brain, are critical for regulating the brain microenvironment. In various neurodegenerative diseases, astrocytes determine the progression and outcome of the neuropathological process. We have recently revealed the direct involvement of mitochondrial function in human pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neuronal differentiation. Using the astroglial-neuronal co-culture system, we show here that astrocytes ...
Source: Stem Cell Reports - January 27, 2018 Category: Stem Cells Source Type: research

Primary Cilia Are Dysfunctional in Obese Adipose-Derived Mesenchymal Stem Cells
Publication date: Available online 27 January 2018 Source:Stem Cell Reports Author(s): Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Samira Catharina Hoock, Susanne Roth, Ulrikke Kielland-Kaisen, Dörthe Brüggmann, Christine Solbach, Frank Louwen, Juping Yuan Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokine...
Source: Stem Cell Reports - January 27, 2018 Category: Stem Cells Source Type: research

Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy
Publication date: Available online 18 January 2018 Source:Stem Cell Reports Author(s): Lara Marrone, Ina Poser, Ian Casci, Julia Japtok, Peter Reinhardt, Antje Janosch, Cordula Andree, Hyun O. Lee, Claudia Moebius, Ellen Koerner, Lydia Reinhardt, Maria Elena Cicardi, Karl Hackmann, Barbara Klink, Angelo Poletti, Simon Alberti, Marc Bickle, Andreas Hermann, Udai Pandey, Anthony A. Hyman, Jared L. Sterneckert Perturbations in stress granule (SG) dynamics may be at the core of amyotrophic lateral sclerosis (ALS). Since SGs are membraneless compartments, modeling their dynamics in human motor neurons has been challenging, thu...
Source: Stem Cell Reports - January 19, 2018 Category: Stem Cells Source Type: research

BAK/BAX-Mediated Apoptosis Is a Myc-Induced Roadblock to  Reprogramming
Publication date: Available online 18 January 2018 Source:Stem Cell Reports Author(s): Esther J.Y. Kim, Minna-Liisa Anko, Christoffer Flensberg, Ian J. Majewski, Fan-Suo Geng, Jaber Firas, David C.S. Huang, Mark F. van Delft, Joan K. Heath Despite intensive efforts to optimize the process, reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most common combination of transcription factors employed comprises OCT4, KLF4, SOX2, and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced further. Cells must overcome several obstacles to reach the pluripotent s...
Source: Stem Cell Reports - January 19, 2018 Category: Stem Cells Source Type: research

MEIS1 Regulates Hemogenic Endothelial Generation, Megakaryopoiesis, and Thrombopoiesis in Human Pluripotent Stem Cells by Targeting TAL1 and FLI1
In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR+ mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs). TAL1 mediates the function of MEIS1 in HEP specification. In addition, MEIS1 is vital for megakaryopoiesis and thrombopoiesis from hPSCs. Mechanistically, FLI1 acts as a downstream gene necessary for the function of MEIS1 during megakaryopoiesis. Thus, MEIS1 controls human hematopoie...
Source: Stem Cell Reports - January 19, 2018 Category: Stem Cells Source Type: research

Recapitulation of Extracellular LAMININ Environment Maintains Stemness of Satellite Cells In  Vitro
In this study, examination of the satellite cell microenvironment in vivo revealed that these cells are encapsulated by LMα2–5. We find that reconstitution of the satellite cell niche with recombinant LM-E8 fragments promotes the proliferation and maintains satellite cells in an undifferentiated state. (Source: Stem Cell Reports)
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

Impact of Swiprosin-1/Efhd2 on Adult Hippocampal Neurogenesis
In this report, Mielenz, Winner, and colleagues show a novel impact of Efhd2 on survival and integration of adult-born hippocampal neurons. This is of particular significance since EFHD2 regulates cytoskeletal transport and synaptic plasticity and since levels of pathological TAU are increased in Efhd2 knockout mice. (Source: Stem Cell Reports)
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

Purification of GFR α1+ and GFRα1– Spermatogonial Stem Cells Reveals a Niche-Dependent Mechanism for Fate Determination
Publication date: Available online 11 January 2018 Source:Stem Cell Reports Author(s): Alina Garbuzov, Matthew F. Pech, Kazuteru Hasegawa, Meena Sukhwani, Ruixuan J. Zhang, Kyle E. Orwig, Steven E. Artandi Undifferentiated spermatogonia comprise a pool of stem cells and progenitor cells that show heterogeneous expression of markers, including the cell surface receptor GFRα1. Technical challenges in isolation of GFRα1+ versus GFRα1– undifferentiated spermatogonia have precluded the comparative molecular characterization of these subpopulations and their functional evaluation as stem cells. Here, we ...
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear Transfer
Publication date: Available online 11 January 2018 Source:Stem Cell Reports Author(s): Degong Ruan, Jiangyun Peng, Xiaoshan Wang, Zhen Ouyang, Qingjian Zou, Yi Yang, Fangbing Chen, Weikai Ge, Han Wu, Zhaoming Liu, Yu Zhao, Bentian Zhao, Quanjun Zhang, Chengdan Lai, Nana Fan, Zhiwei Zhou, Qishuai Liu, Nan Li, Qin Jin, Hui Shi, Jingke Xie, Hong Song, Xiaoyu Yang, Jiekai Chen, Kepin Wang, Xiaoping Li, Liangxue Lai Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely inefficient, and many cloned embryos undergo abnormal development. Here, by profiling transcriptome expression, we observed dysregulated chromos...
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

SOX10 Single Transcription Factor-Based Fast and Efficient Generation of  Oligodendrocytes from Human Pluripotent Stem Cells
In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation. Graphical abstract Teaser In this article, García-León JA and colleagues demonstrate the generation of functional oligodendrocytes (OLs) from human pluripotent stem cells in a rapid and efficient manner by the single overexpression of SOX10. Generated OLs resemble primary OLs at the transcriptome level and can myelinate neurons both in vivo and in vitro. Neuron-OL co-cultures, adapted to high-th...
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

Pathological Endogenous α-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy
Publication date: Available online 11 January 2018 Source:Stem Cell Reports Author(s): Seiji Kaji, Takakuni Maki, Hisanori Kinoshita, Norihito Uemura, Takashi Ayaki, Yasuhiro Kawamoto, Takahiro Furuta, Makoto Urushitani, Masato Hasegawa, Yusuke Kinoshita, Yuichi Ono, Xiaobo Mao, Tran H. Quach, Kazuhiro Iwai, Valina L. Dawson, Ted M. Dawson, Ryosuke Takahashi Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of...
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem  Cells
Publication date: Available online 11 January 2018 Source:Stem Cell Reports Author(s): Sandeep Gupta, Daniel Sivalingam, Samantha Hain, Christian Makkar, Enrique Sosa, Amander Clark, Samantha J. Butler Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory ...
Source: Stem Cell Reports - January 14, 2018 Category: Stem Cells Source Type: research

Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition
Publication date: 9 January 2018 Source:Stem Cell Reports, Volume 10, Issue 1 Author(s): Auston Z. Miller, Alexander Satchie, Alex P. Tannenbaum, Aman Nihal, James A. Thomson, David T. Vereide Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found...
Source: Stem Cell Reports - January 9, 2018 Category: Stem Cells Source Type: research

A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells
Publication date: 9 January 2018 Source:Stem Cell Reports, Volume 10, Issue 1 Author(s): Andreas Kurtz, Stefanie Seltmann, Amos Bairoch, Marie-Sophie Bittner, Kevin Bruce, Amanda Capes-Davis, Laura Clarke, Jeremy M. Crook, Laurence Daheron, Johannes Dewender, Adam Faulconbridge, Wataru Fujibuchi, Alexander Gutteridge, Derek J. Hei, Yong-Ou Kim, Jung-Hyun Kim, Anja Kolb- Kokocinski, Fritz Lekschas, Geoffrey P. Lomax, Jeanne F. Loring, Tenneille Ludwig, Nancy Mah, Tohru Matsui, Robert Müller, Helen Parkinson, Michael Sheldon, Kelly Smith, Harald Stachelscheid, Glyn Stacey, Ian Streeter, Anna Veiga, Ren-He Xu Unambiguou...
Source: Stem Cell Reports - January 9, 2018 Category: Stem Cells Source Type: research

Scarless Genome Editing of Human Pluripotent Stem Cells via Transient Puromycin Selection
We present and characterize a robust method for rapid, scarless introduction or correction of disease-associated variants in hPSCs using CRISPR/Cas9. Utilizing non-integrated plasmid vectors that express a puromycin N-acetyl-transferase (PAC) gene, whose expression and translation is linked to that of Cas9, we transiently select for cells based on their early levels of Cas9 protein. Under optimized conditions, co-delivery with single-stranded donor DNA enabled isolation of clonal cell populations containing both heterozygous and homozygous precise genome edits in as little as 2 weeks without requiring cell sorting or ...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation
Publication date: Available online 4 January 2018 Source:Stem Cell Reports Author(s): Xiaoli Li, Andrew F. Wilson, Wei Du, Qishen Pang Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA). Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC) proliferation in mice deficient for the FA gene Fanca. Deletion of p53 in Fanca −/− mice leads to replicative exhaustion of the hematopoietic stem cell (HSC) in transplant recipients. Using Fanca −/− HSCs expressing the separation-of-functio...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2 α-OCT4/CXCR4 Loop under Hypoxia
Publication date: Available online 4 January 2018 Source:Stem Cell Reports Author(s): Yung-Che Kuo, Heng-Kien Au, Jue-Liang Hsu, Hsiao-Feng Wang, Chiung-Ju Lee, Syue-Wei Peng, Ssu-Chuan Lai, Yu-Chih Wu, Hong-Nerng Ho, Yen-Hua Huang Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC me...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells
Publication date: Available online 4 January 2018 Source:Stem Cell Reports Author(s): Chee Jia Chin, Suwen Li, Mirko Corselli, David Casero, Yuhua Zhu, Chong Bin He, Reef Hardy, Bruno Péault, Gay M. Crooks Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSCs), the capacity of such cells to support hematopoiesis has not been reported. Here, we demonstrate that distinct mesenchymal subpopulations co-emerge from mesoderm during h...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

Real-Time Monitoring of Glutathione in Living Cells Reveals that High Glutathione Levels Are Required to Maintain Stem Cell Function
Publication date: Available online 4 January 2018 Source:Stem Cell Reports Author(s): Eui Man Jeong, Ji-Hye Yoon, Jisun Lim, Ji-Woong Shin, A. Young Cho, Jinbeom Heo, Ki Baek Lee, Jin-Haeng Lee, Won Jong Lee, Hyo-Jun Kim, Young Hoon Son, Seok-Jin Lee, Sung-Yup Cho, Dong-Myung Shin, Kihang Choi, In-Gyu Kim The core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered ...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

Transplanted Donor- or Stem Cell-Derived Cone Photoreceptors Can Both Integrate and Undergo Material Transfer in an Environment-Dependent Manner
Publication date: Available online 4 January 2018 Source:Stem Cell Reports Author(s): Paul V. Waldron, Fabiana Di Marco, Kamil Kruczek, Joana Ribeiro, Anna B. Graca, Claire Hippert, Nozie D. Aghaizu, Aikaterini A. Kalargyrou, Amanda C. Barber, Guilia Grimaldi, Yanai Duran, Samuel J.I. Blackford, Magdalena Kloc, Debbie Goh, Eduardo Zabala Aldunate, Robert D. Sampson, James W.B. Bainbridge, Alexander J. Smith, Anai Gonzalez-Cordero, Jane C. Sowden, Robin R. Ali, Rachael A. Pearson Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photorece...
Source: Stem Cell Reports - January 4, 2018 Category: Stem Cells Source Type: research

Regulation of Mammary Luminal Cell Fate and Tumorigenesis by p38 α
Publication date: Available online 28 December 2017 Source:Stem Cell Reports Author(s): Ivan del Barco Barrantes, Camille Stephan-Otto Attolini, Konstantin Slobodnyuk, Ana Igea, Sara Gregorio, Sylwia Gawrzak, Roger R. Gomis, Angel R. Nebreda Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we have investigated the function of the protein kinase p38α in the mammary gland using mice that delete this protein in the luminal epithelial cells. We show that p38α regulates the fate of luminal progenitor cells through modu...
Source: Stem Cell Reports - December 28, 2017 Category: Stem Cells Source Type: research

TET2 Loss Dysregulates the Behavior of Bone Marrow Mesenchymal Stromal Cells and Accelerates Tet2 −/−-Driven Myeloid Malignancy Progression
In this study, we show that loss of TET2 in BMSCs increases cell proliferation and self-renewal and enhances osteoblast differentiation potential of BMSCs, which may in turn alter their behavior in supporting HSPC proliferation and differentiation. In addition, Tet2 loss alters BMSCs in promoting Tet2-deficiency-mediated myeloid malignancy progression. Tet2 loss in BMSCs also dysregulates hydroxylation of 5-methylcytosine (5mC) and the expression of genes that are key for BMSC proliferation and osteoblast differentiation, leading to alteration of biological characteristics in vivo. These results highlight the critical...
Source: Stem Cell Reports - December 28, 2017 Category: Stem Cells Source Type: research

TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency
Publication date: Available online 28 December 2017 Source:Stem Cell Reports Author(s): Yu Tao, Ming-Ren Yen, Tsotne Chitiashvili, Haruko Nakano, Rachel Kim, Linzi Hosohama, Yao Chang Tan, Atsushi Nakano, Pao-Yang Chen, Amander T. Clark Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE express...
Source: Stem Cell Reports - December 28, 2017 Category: Stem Cells Source Type: research

Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Lei Shi, Lihua Huang, Ruojie He, Weijun Huang, Huiyan Wang, Xingqiang Lai, Zhengwei Zou, Jiaqi Sun, Qiong Ke, Minying Zheng, Xilin Lu, Zhong Pei, Huanxing Su, Andy Peng Xiang, Weiqiang Li, Xiaoli Yao Charcot-Marie-Tooth disease type 1A (CMT1A), one of the most frequent inherited peripheral neuropathies, is associated with PMP22 gene duplication. Previous studies of CMT1A mainly relied on rodent models, and it is not yet clear how PMP22 overexpression leads to the phenotype in patients. Here, we generated the human induced pluripotent s...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

A Phyllopod-Mediated Feedback Loop Promotes Intestinal Stem Cell Enteroendocrine Commitment in Drosophila
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Chang Yin, Rongwen Xi The intestinal epithelium in the Drosophila midgut is maintained by intestinal stem cells (ISCs), which are capable of generating both enterocytes and enteroendocrine cells (EEs) via alternative cell fate specification. Activation of Delta-Notch signaling directs ISCs for enterocyte generation, but how EEs are generated from ISCs remains poorly understood. Here, we identified Phyllopod (Phyl) as a key regulator that drives EE generation from ISCs. Phyl, which is normally suppressed by Notch, functions as an adapto...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

In  Vitro Differentiation of Gata2 and Ly6a Reporter Embryonic Stem Cells Corresponds to In Vivo Waves of Hematopoietic Cell Generation
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Mari-Liis Kauts, Carmen Rodriguez-Seoane, Polynikis Kaimakis, Sandra C. Mendes, Xabier Cortés-Lavaud, Undine Hill, Elaine Dzierzak In vivo hematopoietic generation occurs in waves of primitive and definitive cell emergence. Differentiation cultures of pluripotent embryonic stem cells (ESCs) offer an accessible source of hematopoietic cells for blood-related research and therapeutic strategies. However, despite many approaches, it remains a goal to robustly generate hematopoietic progenitor and stem cells (HP/SCs) in vi...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

Histone 2B-GFP Label-Retaining Prostate Luminal Cells Possess Progenitor Cell Properties and Are Intrinsically Resistant to Castration
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Dingxiao Zhang, Collene Jeter, Shuai Gong, Amanda Tracz, Yue Lu, Jianjun Shen, Dean G. Tang The existence of slow-cycling luminal cells in the prostate has been suggested, but their identity and functional properties remain unknown. Using a bigenic mouse model to earmark, isolate, and characterize the quiescent stem-like cells, we identify a label-retaining cell (LRC) population in the luminal cell layer as luminal progenitors. Molecular and biological characterizations show that these luminal LRCs are significantly enriched in the mou...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Camilla A. Richmond, Hannah Rickner, Manasvi S. Shah, Tracy Ediger, Luke Deary, Fanny Zhou, Alessio Tovaglieri, Diana L. Carlone, David T. Breault The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs) and slowly cycling, reserve ISCs (r-ISCs). Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3
Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Jiajia Zhao, Xin Zhou, Qingming Tang, Ran Yu, Shaoling Yu, Yanlin Long, Cen Cao, Jun Han, Anbing Shi, Jeremy J. Mao, Xiong Chen, Lili Chen Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patien...
Source: Stem Cell Reports - December 21, 2017 Category: Stem Cells Source Type: research

HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Yi Liu, Dong Soon Choi, Jianting Sheng, Joe E. Ensor, Diana Hwang Liang, Cristian Rodriguez-Aguayo, Amanda Polley, Steve Benz, Olivier Elemento, Akanksha Verma, Yang Cong, Helen Wong, Wei Qian, Zheng Li, Sergio Granados-Principal, Gabriel Lopez-Berestein, Melissa D. Landis, Roberto R. Rosato, Bhuvanesh Dave, Stephen Wong, Dario Marchetti, Anil K. Sood, Jenny C. Chang Here, we show that HEMATOLOGICAL AND NEUROLOGICAL EXPRESSED 1-LIKE (HN1L) is a targetable breast cancer stem cell (BCSC) gene that is altered in 25% of whole breast cancer...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Li Wang, Evangelia Koutelou, Calley Hirsch, Ryan McCarthy, Andria Schibler, Kevin Lin, Yue Lu, Collene Jeter, Jianjun Shen, Michelle C. Barton, Sharon Y.R. Dent Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of mul...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

FZD4 Marks Lateral Plate Mesoderm and Signals with NORRIN to Increase Cardiomyocyte Induction from Pluripotent Stem Cell-Derived Cardiac Progenitors
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Charles Yoon, Hannah Song, Ting Yin, Damaris Bausch-Fluck, Andreas P. Frei, Steven Kattman, Nicole Dubois, Alec D. Witty, Johannes A. Hewel, Hongbo Guo, Andrew Emili, Bernd Wollscheid, Gordon Keller, Peter W. Zandstra The identification of cell surface proteins on stem cells or stem cell derivatives is a key strategy for the functional characterization, isolation, and understanding of stem cell population dynamics. Here, using an integrated mass spectrometry- and microarray-based approach, we analyzed the surface proteome and transcrip...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

O-GlcNAc on PKC ζ Inhibits the FGF4-PKCζ-MEK-ERK1/2 Pathway via Inhibition of PKCζ Phosphorylation in Mouse Embryonic Stem Cells
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Taichi Miura, Masahiko Kume, Takeshi Kawamura, Kazuo Yamamoto, Takao Hamakubo, Shoko Nishihara Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiat...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

Impaired IFN γ-Signaling and Mycobacterial Clearance in IFNγR1-Deficient Human iPSC-Derived Macrophages
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Anna-Lena Neehus, Jenny Lam, Kathrin Haake, Sylvia Merkert, Nico Schmidt, Adele Mucci, Mania Ackermann, Madline Schubert, Christine Happle, Mark Philipp Kühnel, Patrick Blank, Friederike Philipp, Ralph Goethe, Danny Jonigk, Ulrich Martin, Ulrich Kalinke, Ulrich Baumann, Axel Schambach, Joachim Roesler, Nico Lachmann Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of interferon gamma (IFNγ) immunity and is characterized by severe infections by weakly virulent mycobacteria. Although IFN&gamm...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

In  Vitro Induction and In Vivo Engraftment of Lung Bud Tip Progenitor Cells Derived from Human Pluripotent Stem Cells
Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Alyssa J. Miller, David R. Hill, Melinda S. Nagy, Yoshiro Aoki, Briana R. Dye, Alana M. Chin, Sha Huang, Felix Zhu, Eric S. White, Vibha Lama, Jason R. Spence The current study aimed to understand the developmental mechanisms regulating bud tip progenitor cells in the human fetal lung, which are present during branching morphogenesis, and to use this information to induce a bud tip progenitor-like population from human pluripotent stem cells (hPSCs) in vitro. We identified cues that maintained isolated human fetal lung epithelial ...
Source: Stem Cell Reports - December 15, 2017 Category: Stem Cells Source Type: research

Contribution of ATOH1+ Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Fumiaki Ishibashi, Hiromichi Shimizu, Toru Nakata, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Sho Anzai, Reiko Kuno, Sayaka Nagata, Go Ito, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1+ secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncert...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research

Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Jack C. Reidling, Aroa Relaño-Ginés, Sandra M. Holley, Joseph Ochaba, Cindy Moore, Brian Fury, Alice Lau, Andrew H. Tran, Sylvia Yeung, Delaram Salamati, Chunni Zhu, Asa Hatami, Carlos Cepeda, Joshua A. Barry, Talia Kamdjou, Alvin King, Dane Coleal-Bergum, Nicholas R. Franich, Frank M. LaFerla, Joan S. Steffan, Mathew Blurton-Jones, Charles K. Meshul, Gerhard Bauer, Michael S. Levine, Marie-Francoise Chesselet, Leslie M. Thompson Huntington's disease (HD) is an inherited neurodegenerative disorder with no disease-modifying...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research

A Refined Culture System for Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Yu Takahashi, Shintaro Sato, Yosuke Kurashima, Tomohisa Yamamoto, Shiho Kurokawa, Yoshikazu Yuki, Naoki Takemura, Satoshi Uematsu, Chen-Yi Lai, Makoto Otsu, Hiroshi Matsuno, Hideki Osawa, Tsunekazu Mizushima, Junichi Nishimura, Mikio Hayashi, Takayuki Yamaguchi, Hiroshi Kiyono Gut epithelial organoids are routinely used to investigate intestinal biology; however, current culture methods are not amenable to genetic manipulation, and it is difficult to generate sufficient numbers for high-throughput studies. Here, we present an improved c...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research

Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Tyler DiStefano, Holly Yu Chen, Christopher Panebianco, Koray Dogan Kaya, Matthew J. Brooks, Linn Gieser, Nicole Y. Morgan, Tom Pohida, Anand Swaroop Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV) bioreactors to culture retinal organoids derived from mouse plurip...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research

Breast Cancers Activate Stromal Fibroblast-Induced Suppression of  Progenitors in Adjacent Normal Tissue
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Sumanta Chatterjee, Pratima Basak, Edward Buchel, Janice Safneck, Leigh C. Murphy, Michael Mowat, Sam K. Kung, Peter Eirew, Connie J. Eaves, Afshin Raouf Human breast cancer cells are known to activate adjacent “normal-like” cells to enhance their own growth, but the cellular and molecular mechanisms involved are poorly understood. We now show by both phenotypic and functional measurements that normal human mammary progenitor cells are significantly under-represented in the mammary epithelium of patients' tumor-adjacent tiss...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research

Generation of Adrenal Chromaffin-like Cells from Human Pluripotent Stem  Cells
Publication date: Available online 7 December 2017 Source:Stem Cell Reports Author(s): Kwaku Dad Abu-Bonsrah, Dongcheng Zhang, Andrew R. Bjorksten, Mirella Dottori, Donald F. Newgreen Adrenomedullary chromaffin cells are catecholamine (CA)-producing cells originating from trunk neural crest (NC) via sympathoadrenal progenitors (SAPs). We generated NC and SAPs from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro via BMP2/FGF2 exposure, ascertained by qPCR and immunoexpression of SOX10, ASCL1, TFAP2α, and PHOX2B, and by fluorescence-activated cell sorting selection for p75NTR...
Source: Stem Cell Reports - December 8, 2017 Category: Stem Cells Source Type: research