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pluripotent stem cell

Clara Lopes Novo, Peter J Rugg-Gunn
Pluripotent cells are characterized by a globally open and accessible chromatin organization that is thought to contribute to cellular plasticity and developmental decision-making. We recently identified the pluripotency factor Nanog as a key regulator of this form of chromatin architecture in mouse embryonic stem cells. In particular, we demonstrated that the transcription factors Nanog and Sall1 co-dependently mediate the epigenetic state of pericentromeric heterochromatin to reinforce a more open and accessible organization in pluripotent cells...
October 19, 2016: Nucleus
Dodanim Talavera-Adame, Orison O Woolcott, Joseph Ignatius-Irudayam, Vaithilingaraja Arumugaswami, David H Geller, Donald C Dafoe
No abstract text is available yet for this article.
October 17, 2016: Diabetologia
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
Whitney A Greene, Teresa A Burke, Elaine D Por, Ramesh R Kaini, Heuy-Ching Wang
Purpose: The purpose of this study was to characterize the secretion profile of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. iPS-RPE was used to develop an in vitro wound healing model. We hypothesized that iPS-RPE secretes cytokines and growth factors which act in an autocrine manner to promote migration and proliferation of cells during wound healing. Methods: iPS-RPE was grown in transwells until fully confluent and pigmented...
August 1, 2016: Investigative Ophthalmology & Visual Science
Orie Hikabe, Nobuhiko Hamazaki, Go Nagamatsu, Yayoi Obata, Yuji Hirao, Norio Hamada, So Shimamoto, Takuya Imamura, Kinichi Nakashima, Mitinori Saitou, Katsuhiko Hayashi
The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts...
October 17, 2016: Nature
Alexandros Strikoudis, Charalampos Lazaris, Thomas Trimarchi, Antonio L Galvao Neto, Yan Yang, Panagiotis Ntziachristos, Scott Rothbart, Shannon Buckley, Igor Dolgalev, Matthias Stadtfeld, Brian D Strahl, Brian D Dynlacht, Aristotelis Tsirigos, Iannis Aifantis
Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf5a) in ESC self-renewal and ascribe its role in regulating pluripotency, cellular reprogramming and myoblast specification. We demonstrate that Phf5a is essential for maintaining pluripotency, since depleted ESCs exhibit hallmarks of differentiation. Mechanistically, we attribute Phf5a function to the stabilization of the Paf1 transcriptional complex and control of RNA polymerase II elongation on pluripotency loci...
October 17, 2016: Nature Cell Biology
Carrie-Ellen Briere, Jacqueline M McGrath, Todd Jensen, Adam Matson, Christine Finck
BACKGROUND: The benefits of breast milk are well described, yet the mechanistic details related to how breast milk protects against acute and chronic diseases and optimizes neurodevelopment remain largely unknown. Recently, breast milk was found to contain stem cells that are thought to be involved in infant development. PURPOSE: The purpose of this review was to synthesize all available research involving the characterization of breast milk stem cells to provide a basis of understanding for what is known and what still needs further exploration...
October 4, 2016: Advances in Neonatal Care: Official Journal of the National Association of Neonatal Nurses
Koichi Okamoto, Itasu Ninomiya, Yoshinao Ohbatake, Atsushi Hirose, Tomoya Tsukada, Shinichi Nakanuma, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Tomoharu Miyashita, Tajima Hidehiro, Hiroyuki Takamura, Sachio Fushida, Tetsuo Ohta
Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC)...
September 28, 2016: Oncology Reports
Elizabeth S Ng, Lisa Azzola, Freya F Bruveris, Vincenzo Calvanese, Belinda Phipson, Katerina Vlahos, Claire Hirst, Vanta J Jokubaitis, Qing C Yu, Jovana Maksimovic, Simone Liebscher, Vania Januar, Zhen Zhang, Brenda Williams, Aude Conscience, Jennifer Durnall, Steven Jackson, Magdaline Costa, David Elliott, David N Haylock, Susan K Nilsson, Richard Saffery, Katja Schenke-Layland, Alicia Oshlack, Hanna K A Mikkola, Edouard G Stanley, Andrew G Elefanty
The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34(+) cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34(+) cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34(+) hematopoietic cells with HOXA expression that more closely resembles that of cord blood...
October 17, 2016: Nature Biotechnology
B Lucendo-Villarin, H Rashidi, K Cameron, D C Hay
Pluripotent stem cell derived liver cells (hepatocytes) represent a promising alternative to primary tissue for biological and clinical applications. To date, most hepatocyte maintenance and differentiation systems have relied upon the use of animal derived components. This serves as a significant barrier to large scale production and application of stem cell derived hepatocytes. Recently, the use of defined biologics has overcome those limitations in two-dimensional monolayer culture. In order to improve the cell phenotype further, three-dimensional culture systems have been employed to better mimic the in vivo situation, drawing upon materials chemistry, engineering and biology...
May 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND AND AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 13, 2016: Journal of Hepatology
Xiaofeng Zheng, Pengyi Yang, Brad Lackford, Brian D Bennett, Li Wang, Hui Li, Yu Wang, Yiliang Miao, Julie F Foley, David C Fargo, Ying Jin, Carmen J Williams, Raja Jothi, Guang Hu
Poly(A) tail length and mRNA deadenylation play important roles in gene regulation. However, how they regulate embryonic development and pluripotent cell fate is not fully understood. Here we present evidence that CNOT3-dependent mRNA deadenylation governs the pluripotent state. We show that CNOT3, a component of the Ccr4-Not deadenylase complex, is required for mouse epiblast maintenance. It is highly expressed in blastocysts and its deletion leads to peri-implantation lethality. The epiblast cells in Cnot3 deletion embryos are quickly lost during diapause and fail to outgrow in culture...
October 8, 2016: Stem Cell Reports
Brigham J Hartley, Kristen J Brennand
Human induced pluripotent stem cells (hiPSCs) can theoretically yield limitless supplies of cells fated to any cell type that comprise the human organism, making them a new tool by which to potentially overcome caveats in current biomedical research. In vitro derivation of central nervous system (CNS) cell types has the potential to provide material for drug discovery and validation, safety and toxicity assays, cell replacement therapy and the elucidation of previously unknown disease mechanisms. However, current two-dimensional (2D) CNS differentiation protocols do not faithfully recapitulate the spatial organization of heterogeneous tissue, nor the cell-cell interactions, cell-extracellular matrix interactions, or specific physiological functions generated within complex tissue such as the brain...
October 12, 2016: Neurochemistry International
E Sacide Çağlayan
Dual-specificity thyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a strong therapeutic target to ameliorate cognitive functions of Down Syndrome (DS). Genetic normalization of Dyrk1a is sufficient to normalize early cortical developmental phenotypes in DS mouse models. Gyrencephalic human neocortical development is more complex than that in lissencephalic mice, hence cerebral organoids (COs) can be used to model early neurodevelopmental defects of DS. Single copy DYRK1A knockout COs (scDYRK1AKO-COs) can be generated from manipulated DS derived (DS-) induced pluripotent stem cells (iPSCs) and genetic normalization of DYRK1A is expected to result in corrected neurodevelopmental phenotypes that can be reminiscent of normal COs...
October 15, 2016: Cell Biology International
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
Seddik Hammad, Hassan Y A H Mahmoud, Lama Hamadneh, Ahmed M Elsherief, Nadja M Meindl-Beinker, Ahmed M Kotb
No abstract text is available yet for this article.
October 14, 2016: Archives of Toxicology
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
: : Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
October 14, 2016: Stem Cells Translational Medicine
Robert F Halliwell
Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine...
October 11, 2016: Neurochemistry International
Shunsuke Tanigawa, Ryuichi Nishinakamura
With recent success in directed differentiation of nephron progenitors from mouse embryonic stem cells or human-induced pluripotent stem cells, the ability to expand these nephron progenitors is an important step toward regenerative medicine in nephrology. A recent publication reports the first successful attempt to propagate human nephron progenitors while retaining their potential to form both glomeruli and renal tubules.
November 2016: Kidney International
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
Our studies investigating the existence of tumor-initiating cell (TIC) populations in human esophageal squamous cell carcinoma (ESCC) had identified a subpopulation of cells isolated from ESCC patient-derived tumor specimens marked by an ALDH(bri+) phenotype bear stem cell-like features. Importantly, KDM4C, a histone demethylase was enhanced in ALDH(bri+) subpopulation, suggesting that strategies interfering with KDM4C may be able to target these putative TICs. In the present study, by genetic and chemical means, we demonstrated that, KDM4C blockade selectively decreased the ESCC ALDH(bri+) TICs population in vitro and specifically targeted the TICs in ALDH(bri+)-derived xenograft, retarding engraftment...
October 2016: Neoplasia: An International Journal for Oncology Research
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