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Stem Cell Reports

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https://www.readbyqxmd.com/read/28919261/top-down-inhibition-of-bmp-signaling-enables-robust-induction-of-hpscs-into-neural-crest-in-fully-defined-xeno-free-conditions
#1
James O S Hackland, Tom J R Frith, Oliver Thompson, Ana Marin Navarro, Martin I Garcia-Castro, Christian Unger, Peter W Andrews
Defects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation...
September 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28919263/single-cell-gene-expression-analysis-of-a-human-esc-model-of-pancreatic-endocrine-development-reveals-different-paths-to-%C3%AE-cell-differentiation
#2
Maja Borup Kjær Petersen, Ajuna Azad, Camilla Ingvorsen, Katja Hess, Mattias Hansson, Anne Grapin-Botton, Christian Honoré
The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells...
September 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28919262/pdgfra-is-not-essential-for-the-derivation-and-maintenance-of-mouse-extraembryonic-endoderm-stem-cell-lines
#3
Jiangwei Lin, Mona Khan, Bolek Zapiec, Peter Mombaerts
Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm lineage. Platelet-derived growth factor receptor alpha (PDGFRA) is thought to be essential for the derivation and maintenance of mouse XEN cell lines. Here, we have re-evaluated this requirement for PDGFRA. We derived multiple PDGFRA-deficient XEN cell lines from postimplantation and preimplantation embryos of a PDGFRA-GFP knockout strain. We also converted PDGFRA-deficient embryonic stem cell lines into XEN cell lines chemically by transient culturing with retinoic acid and Activin A...
September 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28919264/prolactin-alters-the-mammary-epithelial-hierarchy-increasing-progenitors-and-facilitating-ovarian-steroid-action
#4
Kathleen A O'Leary, Michael P Shea, Stephanie Salituro, Courtney E Blohm, Linda A Schuler
Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation...
September 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28919260/blockage-of-the-epithelial-to-mesenchymal-transition-is-required-for-embryonic-stem-cell-derivation
#5
Mehdi Totonchi, Seyedeh-Nafiseh Hassani, Ali Sharifi-Zarchi, Natalia Tapia, Kenjiro Adachi, Julia Arand, Boris Greber, Davood Sabour, Marcos J Araúzo-Bravo, Jörn Walter, Mohammad Pakzad, Hamid Gourabi, Hans R Schöler, Hossein Baharvand
Pluripotent cells emanate from the inner cell mass (ICM) of the blastocyst and when cultivated under optimal conditions immortalize as embryonic stem cells (ESCs). The fundamental mechanism underlying ESC derivation has, however, remained elusive. Recently, we have devised a highly efficient approach for establishing ESCs, through inhibition of the MEK and TGF-β pathways. This regimen provides a platform for dissecting the molecular mechanism of ESC derivation. Via temporal gene expression analysis, we reveal key genes involved in the ICM to ESC transition...
September 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28919259/ontogenic-identification-and-analysis-of-mesenchymal-stromal-cell-populations-during-mouse-limb-and-long-bone-development
#6
Gretel Nusspaumer, Sumit Jaiswal, Andrea Barbero, Robert Reinhardt, Dana Ishay Ronen, Alexander Haumer, Thomas Lufkin, Ivan Martin, Rolf Zeller
Bone-derived mesenchymal stromal cells (MSCs) differentiate into multiple lineages including chondro- and osteogenic fates and function in establishing the hematopoietic compartment of the bone marrow. Here, we analyze the emergence of different MSC types during mouse limb and long bone development. In particular, PDGFRα(pos)SCA-1(pos) (PαS) cells and mouse skeletal stem cells (mSSCs) are detected within the PDGFRα(pos)CD51(pos) (PαCD51) mesenchymal progenitors, which are the most abundant progenitors in early limb buds and developing long bones until birth...
September 1, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28890163/single-stem-cell-imaging-and-analysis-reveals-telomere-length-differences-in%C3%A2-diseased-human-and-mouse-skeletal-muscles
#7
Elisia D Tichy, David K Sidibe, Matthew T Tierney, Michael J Stec, Maryam Sharifi-Sanjani, Harish Hosalkar, Scott Mubarak, F Brad Johnson, Alessandra Sacco, Foteini Mourkioti
Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres...
August 30, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28890164/directed-differentiation-of-human-bone-marrow-stromal-cells-to-fate-committed-schwann-cells
#8
Sa Cai, Yat-Ping Tsui, Kin-Wai Tam, Graham Ka-Hon Shea, Richard Shek-Kwan Chang, Qiang Ao, Daisy Kwok-Yan Shum, Ying-Shing Chan
Our ultimate goal of in vitro derivation of Schwann cells (SCs) from adult bone marrow stromal cells (BMSCs) is such that they may be used autologously to assist post-traumatic nerve regeneration. Existing protocols for derivation of SC-like cells from BMSCs fall short in the stability of the acquired phenotype and the functional capacity to myelinate axons. Our experiments indicated that neuro-ectodermal progenitor cells among the human hBMSCs could be selectively expanded and then induced to differentiate into SC-like cells...
August 29, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28867347/functional-enterospheres-derived-in%C3%A2-vitro-from-human-pluripotent-stem%C3%A2-cells
#9
Rohan R Nadkarni, Soumeya Abed, Brian J Cox, Sonam Bhatia, Jennifer T Lau, Michael G Surette, Jonathan S Draper
Intestinal organoids derived from human pluripotent stem cells (hPSCs) are valuable in vitro research models that enable simplified access to human gastrointestinal tissues. Here, we report the in vitro generation of enterospheres (hEnS) from hPSC-derived gastrointestinal epithelial precursors. hEnS are cystic spheroids with a simple uniform structure composed entirely of intestinal epithelium. hEnS express markers of mature brush border cells and share a transcriptome profile similar to that of more mature intestinal organoids...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28867346/germline-stem-cell-activity-is-sustained-by-sall4-dependent-silencing-of%C3%A2-distinct-tumor-suppressor-genes
#10
Ai-Leen Chan, Hue M La, Julien M D Legrand, Juho-Antti Mäkelä, Michael Eichenlaub, Mia De Seram, Mirana Ramialison, Robin M Hobbs
Sustained spermatogenesis in adult males and fertility recovery following germ cell depletion are dependent on undifferentiated spermatogonia. We previously demonstrated a key role for the transcription factor SALL4 in spermatogonial differentiation. However, whether SALL4 has broader roles within spermatogonia remains unclear despite its ability to co-regulate genes with PLZF, a transcription factor required for undifferentiated cell maintenance. Through development of inducible knockout models, we show that short-term integrity of differentiating but not undifferentiated populations requires SALL4...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28867345/a-pitx3-egfp-reporter-line-reveals-connectivity-of-dopamine-and-non-dopamine-neuronal-subtypes-in-grafts-generated-from-human-embryonic-stem-cells
#11
Jonathan C Niclis, Carlos W Gantner, Cameron P J Hunt, Jessica A Kauhausen, Jennifer C Durnall, John M Haynes, Colin W Pouton, Clare L Parish, Lachlan H Thompson
Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28867344/nk-cell-alloreactivity-against-kir-ligand-mismatched-hla-haploidentical-tissue-derived-from-hla-haplotype-homozygous-ipscs
#12
Hiroshi Ichise, Seiji Nagano, Takuya Maeda, Masaki Miyazaki, Yuki Miyazaki, Hiroto Kojima, Nobuyo Yawata, Makoto Yawata, Hidenori Tanaka, Hiroh Saji, Kyoko Masuda, Hiroshi Kawamoto
HLA haplotype-homozygous (HLA-homo) induced pluripotent stem cells (iPSCs) are being prepared to be used for allogeneic transplantation of regenerated tissue into recipients carrying an identical haplotype in one of the alleles (HLA-hetero). However, it remains unaddressed whether natural killer (NK) cells respond to these regenerated cells. HLA-C allotypes, known to serve as major ligands for inhibitory receptors of NK cells, can be classified into group 1 (C1) and group 2 (C2), based on their binding specificities...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28844660/dermatopontin-in-bone-marrow-extracellular-matrix-regulates-adherence-but-is-dispensable-for-murine-hematopoietic-cell-maintenance
#13
Ashley C Kramer, Amanda L Blake, Mandy E Taisto, Michael J Lehrke, Beau R Webber, Troy C Lund
The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. We generated constitutional DPT(-/-) mice that were viable and had no peripheral lympho-hematopoietic abnormalities...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28844659/recapitulation-of-human-retinal-development-from-human-pluripotent-stem-cells-generates-transplantable-populations-of-cone-photoreceptors
#14
Anai Gonzalez-Cordero, Kamil Kruczek, Arifa Naeem, Milan Fernando, Magdalena Kloc, Joana Ribeiro, Debbie Goh, Yanai Duran, Samuel J I Blackford, Laura Abelleira-Hervas, Robert D Sampson, Ian O Shum, Matthew J Branch, Peter J Gardner, Jane C Sowden, James W B Bainbridge, Alexander J Smith, Emma L West, Rachael A Pearson, Robin R Ali
Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28844658/direct-reprogramming-of-resident-ng2-glia-into-neurons-with-properties-of-fast-spiking-parvalbumin-containing-interneurons
#15
Maria Pereira, Marcella Birtele, Shelby Shrigley, Julio Aguila Benitez, Eva Hedlund, Malin Parmar, Daniella Rylander Ottosson
Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. Here, we show that neurons reprogrammed using Ascl1, Lmx1a, and Nurr1 functionally mature and integrate into existing brain circuitry and that the majority of the reprogrammed neurons have properties of fast-spiking, parvalbumin-containing interneurons...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28844657/cytoplasmic-and-nuclear-taz-exert-distinct-functions-in-regulating-primed%C3%A2-pluripotency
#16
Xingliang Zhou, Jean Paul Chadarevian, Bryan Ruiz, Qi-Long Ying
Mouse epiblast stem cells (mEpiSCs) and human embryonic stem cells (hESCs) are primed pluripotent stem cells whose self-renewal can be maintained through cytoplasmic stabilization and retention of β-catenin. The underlying mechanism, however, remains largely unknown. Here, we show that cytoplasmic β-catenin interacts with and retains TAZ, a Hippo pathway effector, in the cytoplasm. Cytoplasmic retention of TAZ promotes mEpiSC self-renewal in the absence of nuclear β-catenin, whereas nuclear translocation of TAZ induces mEpiSC differentiation...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28844656/methylome-analysis-of-human-bone-marrow-mscs-reveals-extensive-age-and-culture-induced-changes-at-distal-regulatory-elements
#17
Kalyan K Pasumarthy, Naresh Doni Jayavelu, Lotta Kilpinen, Colin Andrus, Stephanie L Battle, Matti Korhonen, Petri Lehenkari, Riikka Lund, Saara Laitinen, R David Hawkins
Human bone marrow stromal cells, or mesenchymal stem cells (BM-MSCs), need expansion prior to use as cell-based therapies in immunological and tissue repair applications. Aging and expansion of BM-MSCs induce epigenetic changes that can impact therapeutic outcomes. By applying sequencing-based methods, we reveal that the breadth of DNA methylation dynamics associated with aging and expansion is greater than previously reported. Methylation changes are enriched at known distal transcription factor binding sites such as enhancer elements, instead of CpG-rich regions, and are associated with changes in gene expression...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28826853/inhibition-of-ezh2-promotes-human-embryonic-stem-cell-differentiation-into-mesoderm-by-reducing-h3k27me3
#18
Yongxin Yu, Peng Deng, Bo Yu, John M Szymanski, Tara Aghaloo, Christine Hong, Cun-Yu Wang
Mesoderm derived from human embryonic stem cells (hESCs) is a major source of the mesenchymal stem/stromal cells (MSCs) that can differentiate into osteoblasts and chondrocytes for tissue regeneration. While significant progress has been made in understanding of molecular mechanisms of hESC differentiation into mesodermal cells, little is known about epigenetic factors controlling hESC fate toward mesoderm and MSCs. Identifying potential epigenetic factors that control hESC differentiation will undoubtedly lead to advancements in regenerative medicine...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28826852/enhanced-dentate-neurogenesis-after-brain-injury-undermines-long-term-neurogenic-potential-and-promotes-seizure-susceptibility
#19
Eric J Neuberger, Bogumila Swietek, Lucas Corrubia, Anagha Prasanna, Vijayalakshmi Santhakumar
Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28826851/jmjd1c-ensures-mouse-embryonic-stem-cell-self-renewal-and-somatic-cell-reprogramming-through-controlling-microrna-expression
#20
Feng Xiao, Bing Liao, Jing Hu, Shuang Li, Haixin Zhao, Ming Sun, Junjie Gu, Ying Jin
The roles of histone demethylases (HDMs) for the establishment and maintenance of pluripotency are incompletely characterized. Here, we show that JmjC-domain-containing protein 1c (JMJD1C), an H3K9 demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and epithelial-to-mesenchymal transition (EMT) to induce differentiation of ESCs. Inhibition of ERK/MAPK signaling rescues the differentiation phenotype caused by Jmjd1c depletion...
September 12, 2017: Stem Cell Reports
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