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human embryonic stem cells

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https://www.readbyqxmd.com/read/28820907/positive-regulatory-interactions-between-yap-and-hedgehog-signalling-in-skin-homeostasis-and-bcc-development-in-mouse-skin-in-vivo
#1
Bassem Akladios, Veronica Mendoza Reinoso, Jason E Cain, Taopeng Wang, Duncan L Lambie, D Neil Watkins, Annemiek Beverdam
Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury. YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis. However, the genetic contexts in which they act to control tissue homeostasis remain mostly unresolved. We provide compelling evidence that epidermal YAP and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity...
2017: PloS One
https://www.readbyqxmd.com/read/28818098/sex-chromosomes-drive-gene-expression-and-regulatory-dimorphisms-in-mouse-embryonic-stem-cells
#2
Rachael J Werner, Bryant M Schultz, Jacklyn M Huhn, Jaroslav Jelinek, Jozef Madzo, Nora Engel
BACKGROUND: Pre-implantation embryos exhibit sexual dimorphisms in both primates and rodents. To determine whether these differences reflected sex-biased expression patterns, we generated transcriptome profiles for six 40,XX, six 40,XY, and two 39,X mouse embryonic stem (ES) cells by RNA sequencing. RESULTS: We found hundreds of coding and non-coding RNAs that were differentially expressed between male and female cells. Surprisingly, the majority of these were autosomal and included RNA encoding transcription and epigenetic and chromatin remodeling factors...
August 17, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28815178/stem-cell-manipulation-gene-therapy-and-the-risk-of-cancer-stem-cell-emergence
#3
REVIEW
Flora Clément, Elodie Grockowiak, Florence Zylbersztejn, Gaëlle Fossard, Stéphanie Gobert, Véronique Maguer-Satta
Stem cells (SCs) have been extensively studied in the context of regenerative medicine. Human hematopoietic stem cell (HSC)-based therapies have been applied to treat leukemic patients for decades. Handling of mesenchymal stem cells (MSCs) has also raised hopes and concerns in the field of tissue engineering. Lately, discovery of cell reprogramming by Yamanaka's team has profoundly modified research strategies and approaches in this domain. As we gain further insight into cell fate mechanisms and identification of key actors and parameters, this also raises issues as to the manipulation of SCs...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28815176/strategies-for-retinal-cell-generation-from-human-pluripotent-stem-cells
#4
REVIEW
Lindsey S Weed, Jason A Mills
Induced pluripotent stem cells (iPSCs) are specialized self-renewing cells that are generated by exogenously expressing pluripotency-associated transcription factors in somatic cells such as fibroblasts, peripheral blood mononuclear cells, or lymphoblastoid cell lines (LCLs). iPSCs are functionally similar to naturally pluripotent embryonic stem cells (ESCs) in their capacity to propagate indefinitely and potential to differentiate into all human cell types, and are devoid of the associated ethical complications of origin...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28814648/zc4h2-stabilizes-smads-to-enhance-bmp-signalling-which-is-involved-in-neural-development-in-xenopus
#5
Pengcheng Ma, Biyu Ren, Xiangcai Yang, Bin Sun, Xiaoliang Liu, Qinghua Kong, Chaocui Li, Bingyu Mao
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28813672/chromatin-and-transcriptional-analysis-of-mesoderm-progenitor-cells-identifies-hopx-as-a-regulator-of-primitive-hematopoiesis
#6
Nathan J Palpant, Yuliang Wang, Brandon Hadland, Rebecca J Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813511/differentiation-of-human-embryonic-stem-cells-into-corneal-epithelial-progenitor-cells-under-defined-conditions
#7
Canwei Zhang, Liqun Du, Kunpeng Pang, Xinyi Wu
The development of cell-based therapies using stem cells represents a significant breakthrough in the treatment of limbal stem cell deficiency (LSCD). The aim of this study was to develop a novel protocol to differentiate human embryonic stem cells (hESCs) into corneal epithelial progenitor cells (CEPCs), with similar features to primary cultured human limbal stem cells (LSCs), using a medium composed of DMEM/F12 and defined keratinocyte serum-free medium (KSFM) (1:1) under different carbon dioxide (CO2) levels in culture...
2017: PloS One
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#8
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812219/eminent-sources-of-adult-mesenchymal-stem-cells-and-their-therapeutic-imminence
#9
REVIEW
Dannie Macrin, Joel P Joseph, Aruthra Arumugam Pillai, Arikketh Devi
In the recent times, stem cell biology has garnered the attention of the scientific fraternity and the general public alike due to the immense therapeutic potential that it holds in the field of regenerative medicine. A breakthrough in this direction came with the isolation of stem cells from human embryo and their differentiation into cell types of all three germ layers. However, the isolation of mesenchymal stem cells from adult tissues proved to be advantageous over embryonic stem cells due to the ethical and immunological naivety...
August 15, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28811661/myst2-kat7-histone-acetyltransferase-interaction-proteomics-reveals-tumour-suppressor-niam-as-a-novel-binding-partner-in-embryonic-stem-cells
#10
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811218/wnt-signaling-positively-regulates-endothelial-cell-fate-specification-in-the-fli1a-positive-progenitor-population-via-lef1
#11
Kathleen Hübner, Kathrin S Grassme, Jyoti Rao, Nina K Wenke, Cordula L Zimmer, Laura Korte, Katja Mu Ller, Saulius Sumanas, Boris Greber, Wiebke Herzog
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)(mu288); Tg(14TCF:loxP-STOP-loxP-dGFP)(mu202))...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28808015/a-p53-dependent-response-limits-the-viability-of-mammalian-haploid-cells
#12
Teresa Olbrich, Cristina Mayor-Ruiz, Maria Vega-Sendino, Carmen Gomez, Sagrario Ortega, Sergio Ruiz, Oscar Fernandez-Capetillo
The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807034/exosomes-from-embryonic-mesenchymal-stem-cells-alleviate-osteoarthritis-through-balancing-synthesis-and-degradation-of-cartilage-extracellular-matrix
#13
Yafei Wang, Dongsheng Yu, Zhiming Liu, Fang Zhou, Jun Dai, Bingbing Wu, Jing Zhou, Boon Chin Heng, Xiao Hui Zou, Hongwei Ouyang, Hua Liu
BACKGROUND: Mesenchymal stem cell therapy for osteoarthritis (OA) has been widely investigated, but the mechanisms are still unclear. Exosomes that serve as carriers of genetic information have been implicated in many diseases and are known to participate in many physiological processes. Here, we investigate the therapeutic potential of exosomes from human embryonic stem cell-induced mesenchymal stem cells (ESC-MSCs) in alleviating osteoarthritis (OA). METHODS: Exosomes were harvested from conditioned culture media of ESC-MSCs by a sequential centrifugation process...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28806594/signaling-networks-in-the-control-of-pluripotency
#14
REVIEW
Hanzhi Zhao, Ying Jin
Embryonic stem cells (ESCs) are characterized by their ability of unlimited self-renewal in vitro and pluripotent developmental potential, which endows them with great values in basic research and future clinical application. However, realization of full potential of ESCs is dependent on the elucidation of molecular mechanisms governing ESCs, among which signaling pathways play critical roles. A great deal of efforts has been made in the past decades to understand what and how signaling pathways contribute to the establishment and maintenance of pluripotency...
August 11, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28806172/mobilization-of-line-1-retrotransposons-is-restricted-by-tex19-1-in-mouse-embryonic-stem-cells
#15
Marie MacLennan, Marta García-Cañadas, Judith Reichmann, Elena Khazina, Gabriele Wagner, Christopher J Playfoot, Carmen Salvador-Palomeque, Abigail R Mann, Paula Peressini, Laura Sanchez, Karen Dobie, David Read, Chao-Chun Hung, Ragnhild Eskeland, Richard R Meehan, Oliver Weichenrieder, Jose Luis García-Pérez, Ian R Adams
Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28803914/targeted-disruption-of-tcf12-reveals-heb-as-essential-in-human-mesodermal-specification-and-hematopoiesis
#16
Yang Li, Patrick M Brauer, Jastaranpreet Singh, Sintia Xhiku, Kogulan Yoganathan, Juan Carlos Zúñiga-Pflücker, Michele K Anderson
Hematopoietic stem cells arise from mesoderm-derived hemogenic endothelium (HE) during embryogenesis in a process termed endothelial-hematopoietic transition (EHT). To better understand the gene networks that control this process, we investigated the role of the transcription factor HEB (TCF12) by disrupting the TCF12 gene locus in human embryonic stem cells (hESCs) and inducing them to differentiate toward hematopoietic outcomes. HEB-deficient hESCs retained key features of pluripotency, including expression of SOX2 and SSEA-4 and teratoma formation, while NANOG expression was reduced...
August 2, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28800962/contacting-co-culture-of-human-retinal-microvascular-endothelial-cells-alters-barrier-function-of-human-embryonic-stem-cell-derived-retinal-pigment-epithelial-cells
#17
H Skottman, J Muranen, H Lähdekorpi, E Pajula, K Mäkelä, L Koivusalo, A Koistinen, H Uusitalo, K Kaarniranta, K Juuti-Uusitalo
Here we evaluated the effects of human retinal microvascular endothelial cells (hREC) on mature human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells. The hESC-RPE cells (Regea08/017, Regea08/023 or Regea11/013) and hREC (ACBRI 181) were co-cultured on opposite sides of transparent membranes for up to six weeks. Thereafter barrier function, small molecule permeability, localization of RPE and endothelial cell marker proteins, cellular fine structure, and growth factor secretion of were evaluated...
August 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28796841/single-cell-qpcr-reveals-that-additional-hand2-and-microrna-1-facilitate-the-early-reprogramming-progress-of-seven-factor-induced-human-myocytes
#18
Emre Bektik, Adrienne Dennis, Prateek Prasanna, Anant Madabhushi, Ji-Dong Fu
The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28795648/human-embryonic-stem-cell-derived-cardiomyocytes-self-arrange-with-areas-of-different-subtypes-during-differentiation
#19
Maj Linea Vestergaard, Søren J Grubb, Karen Koefod Rasmussen, Zoe Anderson-Jenkins, Kristina Grunnet-Lauridsen, Kristine Calloe, Christian Clausen, Søren T Christensen, Kjeld Møllgård, Claus Yding Andersen
The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESC) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of CMs derived from hESCs (hESC-CMs) and examined how the expression of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2...
August 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28794185/id-genes-are-essential-for-early-heart-formation
#20
Thomas J Cunningham, Michael S Yu, Wesley L McKeithan, Sean Spiering, Florent Carrette, Chun-Teng Huang, Paul J Bushway, Matthew Tierney, Sonia Albini, Mauro Giacca, Miguel Mano, Pier Lorenzo Puri, Alessandra Sacco, Pilar Ruiz-Lozano, Jean-Francois Riou, Muriel Umbhauer, Gregg Duester, Mark Mercola, Alexandre R Colas
Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix-loop-helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation-Tcf3 and Foxa2-and activating inducers Evx1, Grrp1, and Mesp1...
August 9, 2017: Genes & Development
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