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Stem Cell Reports

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https://www.readbyqxmd.com/read/28625536/reconstructing-lineage-hierarchies-of-mouse-uterus-epithelial-development-using-single-cell-analysis
#1
Bingbing Wu, Chengrui An, Yu Li, Zi Yin, Lin Gong, Zhenli Li, Yixiao Liu, Boon Chin Heng, Dandan Zhang, Hongwei Ouyang, Xiaohui Zou
The endometrial layer comprises luminal and glandular epithelia that both develop from the same simple layer of fetal uterine epithelium. Mechanisms of uterine epithelial progenitor self-renewal and differentiation are unclear. This study aims to systematically analyze the molecular and cellular mechanisms of uterine epithelial development by single-cell analysis. An integrated set of single-cell transcriptomic data of uterine epithelial progenitors and their differentiated progenies is provided. Additionally the unique molecular signatures of these cells, characterized by sequential upregulation of specific epigenetic and metabolic activities, and activation of unique signaling pathways and transcription factors, were also investigated...
June 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28625538/a-strong-contractile-actin-fence-and-large-adhesions-direct-human-pluripotent-colony-morphology-and-adhesion
#2
Elisa Närvä, Aki Stubb, Camilo Guzmán, Matias Blomqvist, Diego Balboa, Martina Lerche, Markku Saari, Timo Otonkoski, Johanna Ivaska
Cell-type-specific functions and identity are tightly regulated by interactions between the cell cytoskeleton and the extracellular matrix (ECM). Human pluripotent stem cells (hPSCs) have ultimate differentiation capacity and exceptionally low-strength ECM contact, yet the organization and function of adhesion sites and associated actin cytoskeleton remain poorly defined. We imaged hPSCs at the cell-ECM interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers...
June 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28625537/the-developmental-stage-of-adult-human-stem-cell-derived-retinal-pigment-epithelium-cells-influences-transplant-efficacy-for-vision-rescue
#3
Richard J Davis, Nazia M Alam, Cuiping Zhao, Claudia Müller, Janmeet S Saini, Timothy A Blenkinsop, Francesca Mazzoni, Melissa Campbell, Susan M Borden, Carol J Charniga, Patty L Lederman, Vanessa Aguilar, Michael Naimark, Michael Fiske, Nathan Boles, Sally Temple, Silvia C Finnemann, Glen T Prusky, Jeffrey H Stern
Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue...
June 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28625535/glial-specific-functions-of-microcephaly-protein-wdr62-and-interaction-with-the-mitotic-kinase-aurka-are-essential-for-drosophila-brain-growth
#4
Nicholas R Lim, Belal Shohayeb, Olga Zaytseva, Naomi Mitchell, S Sean Millard, Dominic C H Ng, Leonie M Quinn
The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume...
June 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28602614/mir-203-interplays-with-polycomb-repressive-complexes-to-regulate-the-proliferation-of-neural-stem-progenitor-cells
#5
Pei-Pei Liu, Gang-Bin Tang, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Hong-Zhen Du, Zhao-Qian Teng, Chang-Mei Liu
The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28602613/cryopause-a-new-method-to-immediately-initiate-experiments-after-cryopreservation-of-pluripotent-stem-cells
#6
Karen G Wong, Sean D Ryan, Kiran Ramnarine, Siera A Rosen, Shannon E Mann, Amanda Kulick, Elisa De Stanchina, Franz-Josef Müller, Thadeous J Kacmarczyk, Chao Zhang, Doron Betel, Mark J Tomishima
Human pluripotent stem cells (PSCs) provide an unlimited cell source for cell therapies and disease modeling. Despite their enormous power, technical aspects have hampered reproducibility. Here, we describe a modification of PSC workflows that eliminates a major variable for nearly all PSC experiments: the quality and quantity of the PSC starting material. Most labs continually passage PSCs and use small quantities after expansion, but the "just-in-time" nature of these experiments means that quality control rarely happens before use...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28602615/pten-mediates-activation-of-core-clock-protein-bmal1-and-accumulation-of-epidermal-stem-cells
#7
Chiara Zagni, Luciana O Almeida, Tarek Balan, Marco T Martins, Luciana K Rosselli-Murai, Petros Papagerakis, Rogerio M Castilho, Cristiane H Squarize
Tissue integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. In the skin, hair follicle stem cells (HFSCs) that reside within the bulge maintain tissue homeostasis in response to activating cues that occur with each new hair cycle or upon injury. We found that PTEN, a major regulator of the PI3K-AKT pathway, controlled HFSC number and size in the bulge and maintained genomically stable pluripotent cells. This regulatory function is central for HFSC quiescence, where PTEN-deficiency phenotype is in part regulated by BMAL1...
June 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28602612/lineage-reprogramming-of-astroglial-cells-from-different-origins-into-distinct-neuronal-subtypes
#8
Malek Chouchane, Ana Raquel Melo de Farias, Daniela Maria de Sousa Moura, Markus Michael Hilscher, Timm Schroeder, Richardson Naves Leão, Marcos Romualdo Costa
Astroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs) in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2) or Achaete scute homolog-1 (Ascl1). We show that cerebellum (CerebAstro) and cerebral cortex astroglia (CtxAstro) generates iNs with distinctive neurochemical and morphological properties...
June 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28602611/dna-methyltransferases-modulate-hepatogenic-lineage-plasticity-of%C3%A2-mesenchymal-stromal-cells
#9
Chien-Wei Lee, Wei-Chih Huang, Hsien-Da Huang, Yi-Hsiang Huang, Jennifer H Ho, Muh-Hwa Yang, Vincent W Yang, Oscar K Lee
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor β1 (TGFβ1), which in turn controls hepatogenic differentiation and de-differentiation...
June 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579393/long-noncoding-rna-moderates-microrna-activity-to-maintain-self-renewal-in-embryonic-stem-cells
#10
Keriayn N Smith, Joshua Starmer, Sarah C Miller, Praveen Sethupathy, Terry Magnuson
Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the pluripotent state. In ESCs, Cyrano is a stably expressed long intergenic noncoding RNA with no previously assigned role. We demonstrate that Cyrano contributes to ESC maintenance, as its depletion results in the loss of hallmarks of self-renewal. Delineation of Cyrano's network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ESC maintenance...
May 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28552604/evidence-of-in%C3%A2-vitro-preservation-of-human-nephrogenesis-at-the-single-cell-level
#11
Naomi Pode-Shakked, Rotem Gershon, Gal Tam, Dorit Omer, Yehudit Gnatek, Itamar Kanter, Sarit Oriel, Guy Katz, Orit Harari-Steinberg, Tomer Kalisky, Benjamin Dekel
During nephrogenesis, stem/progenitor cells differentiate and give rise to early nephron structures that segment to proximal and distal nephron cell types. Previously, we prospectively isolated progenitors from human fetal kidney (hFK) utilizing a combination of surface markers. However, upon culture nephron progenitors differentiated and could not be robustly maintained in vitro. Here, by culturing hFK in a modified medium used for in vitro growth of mouse nephron progenitors, and by dissection of NCAM(+)/CD133(-) progenitor cells according to EpCAM expression (NCAM(+)/CD133(-)/EpCAM(-), NCAM(+)/CD133(-)/EpCAM(dim), NCAM(+)/CD133(-)/EpCAM(bright)), we show at single-cell resolution a preservation of uninduced and induced cap mesenchyme as well as a transitioning mesenchymal-epithelial state...
May 25, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579395/cryopreservation-maintains-functionality-of-human-ipsc-dopamine-neurons-and-rescues-parkinsonian-phenotypes-in%C3%A2-vivo
#12
Dustin R Wakeman, Benjamin M Hiller, David J Marmion, Christopher W McMahon, Grant T Corbett, Kile P Mangan, Junyi Ma, Lauren E Little, Zhong Xie, Tamara Perez-Rosello, Jaime N Guzman, D James Surmeier, Jeffrey H Kordower
A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579394/primate-primordial-germ-cells-acquire-transplantation-potential-by-carnegie-stage-23
#13
Amander T Clark, Sofia Gkountela, Di Chen, Wanlu Liu, Enrique Sosa, Meena Sukhwani, Jon D Hennebold, Kyle E Orwig
Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579396/thap1-role-in-mouse-embryonic-stem-cell-survival-and-differentiation
#14
Francesca Aguilo, Zuchra Zakirova, Katie Nolan, Ryan Wagner, Rajal Sharma, Megan Hogan, Chengguo Wei, Yifei Sun, Martin J Walsh, Kevin Kelley, Weijia Zhang, Laurie J Ozelius, Pedro Gonzalez-Alegre, Thomas P Zwaka, Michelle E Ehrlich
THAP1 (THAP [Thanatos-associated protein] domain-containing, apoptosis-associated protein 1) is a ubiquitously expressed member of a family of transcription factors with highly conserved DNA-binding and protein-interacting regions. Mutations in THAP1 cause dystonia, DYT6, a neurologic movement disorder. THAP1 downstream targets and the mechanism via which it causes dystonia are largely unknown. Here, we show that wild-type THAP1 regulates embryonic stem cell (ESC) potential, survival, and proliferation. Our findings identify THAP1 as an essential factor underlying mouse ESC survival and to some extent, differentiation, particularly neuroectodermal...
May 19, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528701/expansion-and-purification-are-critical-for-the-therapeutic-application-of-pluripotent-stem-cell-derived-myogenic-progenitors
#15
Jaemin Kim, Alessandro Magli, Sunny S K Chan, Vanessa K P Oliveira, Jianbo Wu, Radbod Darabi, Michael Kyba, Rita C R Perlingeiro
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528699/steps-toward-maturation-of-embryonic-stem-cell-derived-cardiomyocytes-by-defined-physical-signals
#16
Nian Shen, Anne Knopf, Claas Westendorf, Udo Kraushaar, Julia Riedl, Hannah Bauer, Simone Pöschel, Shannon Lee Layland, Monika Holeiter, Stefan Knolle, Eva Brauchle, Ali Nsair, Svenja Hinderer, Katja Schenke-Layland
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28552602/classification-and-functional-characterization-of-vasa-vasorum-associated-perivascular-progenitor-cells-in-human-aorta
#17
Marie Billaud, Vera S Donnenberg, Bradley W Ellis, E Michael Meyer, Albert D Donnenberg, Jennifer C Hill, Tara D Richards, Thomas G Gleason, Julie A Phillippi
In the microcirculation, pericytes are believed to function as mesenchymal stromal cells (MSCs). We hypothesized that the vasa vasorum harbor progenitor cells within the adventitia of human aorta. Pericytes, endothelial progenitor cells, and other cell subpopulations were detected among freshly isolated adventitial cells using flow cytometry. Purified cultured pericytes were enriched for the MSC markers CD105 and CD73 and depleted of the endothelial markers von Willebrand factor and CD31. Cultured pericytes were capable of smooth muscle lineage progression including inducible expression of smooth muscle myosin heavy chain, calponin, and α-smooth muscle actin, and adopted a spindle shape...
May 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579392/bptf-maintains-chromatin-accessibility-and-the-self-renewal-capacity-of-mammary-gland-stem-cells
#18
Wesley D Frey, Anisha Chaudhry, Priscila F Slepicka, Adam M Ouellette, Steven E Kirberger, William C K Pomerantz, Gregory J Hannon, Camila O Dos Santos
Chromatin remodeling is a key requirement for transcriptional control of cellular differentiation. However, the factors that alter chromatin architecture in mammary stem cells (MaSCs) are poorly understood. Here, we show that BPTF, the largest subunit of the NURF chromatin remodeling complex, is essential for MaSC self-renewal and differentiation of mammary epithelial cells (MECs). BPTF depletion arrests cells at a previously undefined stage of epithelial differentiation that is associated with an incapacity to achieve the luminal cell fate...
May 16, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28579391/a-rho-small-gtpase-regulator-abr-secures-mitotic-fidelity-in-human-embryonic-stem-cells
#19
Masatoshi Ohgushi, Maki Minaguchi, Mototsugu Eiraku, Yoshiki Sasai
Pluripotent stem cells can undergo repeated self-renewal while retaining genetic integrity, but they occasionally acquire aneuploidy during long-term culture, which is a practical obstacle for medical applications of human pluripotent stem cells. In this study, we explored the biological roles of ABR, a regulator of RHO family small GTPases, and found that it has pivotal roles during mitotic processes in human embryonic stem cells (hESCs). Although ABR has been shown to be involved in dissociation-induced hESC apoptosis, it does not appear to have direct effects on cell survival unless cell-cell contact is impaired...
May 15, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506532/accreditation-of-biosafe-clinical-grade-human-embryonic-stem-cells-according-to-chinese-regulations
#20
Qi Gu, Juan Wang, Lei Wang, Zheng-Xin Liu, Wan-Wan Zhu, Yuan-Qing Tan, Wei-Fang Han, Jun Wu, Chun-Jing Feng, Jin-Hui Fang, Lei Liu, Liu Wang, Wei Li, Xiao-Yang Zhao, Bao-Yang Hu, Jie Hao, Qi Zhou
Human embryonic stem cells (hESCs) are promising in regenerative medicine. Although several hESC-based clinical trials are under way, a widely accepted standard of clinical-grade cells remains obscure. To attain a completely xeno-free clinical-grade cell line, the system must be free of xenogenic components, the cells must have a comprehensive set of functions, and good manufacturing practice conditions must be used. In this study, following these criteria, we successfully derived two hESC lines, which were thereby considered "clinical-grade embryonic stem cells"...
May 11, 2017: Stem Cell Reports
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