Tracking the embryonic stem cell transition from ground state pluripotency.
Tüzer Kalkan,Nelly Olova,Mila Roode,Carla Mulas,Heather J. Lee,Heather J. Lee,Isabelle Nett,Hendrik Marks,Rachael C. Walker,Rachael C. Walker,Hendrik G. Stunnenberg,Kathryn S. Lilley,Jennifer Nichols,Jennifer Nichols,Wolf Reik,Wolf Reik,Wolf Reik,Paul Bertone,Austin Smith,Austin Smith +19 more
TLDR
The initial transition process for extinction of mouse embryonic stem cell identity upon differentiation immediately follows collapse of the naïve pluripotency transcription factor circuitry and precedes upregulation of lineage-specific factors.Abstract:
Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here, we examine the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naive pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naive cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.read more
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Epigenetic resetting of human pluripotency.
Ge Guo,Ferdinand von Meyenn,Maria Rostovskaya,James Clarke,Sabine Dietmann,Duncan Baker,Anna Sahakyan,Samuel Myers,Paul Bertone,Wolf Reik,Wolf Reik,Wolf Reik,Kathrin Plath,Austin Smith +13 more
TL;DR: A simple, transgene-free method is described for resetting human ESCs or iPSCs to a stable naïve status via transient histone deacetylase inhibition.
Continuum:越多元,越精彩
TL;DR: In this paper, the authors describe a system called Continuum, which is a "continuum" consisting of a series of "continuities" including: 1.1983年成立,随后在米兰、首尔开设办公室 ,2009年将版图拓
Journal ArticleDOI
Pluripotent state transitions coordinate morphogenesis in mouse and human embryos
Marta N. Shahbazi,Antonio Scialdone,Natalia Skorupska,Antonia Weberling,Gaëlle Recher,Meng Zhu,Agnieszka Jedrusik,Liani Devito,Laila Noli,Iain C. Macaulay,Christa Buecker,Y. Khalaf,Dusko Ilic,Thierry Voet,Thierry Voet,John C. Marioni,John C. Marioni,John C. Marioni,Magdalena Zernicka-Goetz +18 more
TL;DR: It is shown that exit from an unrestricted naive pluripotent state is required for epiblast epithelialization and generation of the pro-amniotic cavity in mouse embryos and the relevance of transitions between these states during development of the mammalian embryo is shown.
Journal ArticleDOI
Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development.
Thorsten Boroviak,Giuliano Giuseppe Stirparo,Sabine Dietmann,Irene Hernando-Herraez,Hisham Mohammed,Wolf Reik,Austin Smith,Erika Sasaki,Jennifer Nichols,Paul Bertone +9 more
TL;DR: This cross-species analysis demarcates both conserved and primate-specific features of preimplantation development, and underscores the molecular adaptability of early mammalian embryogenesis.
Journal ArticleDOI
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning
Sophie M. Morgani,Sophie M. Morgani,Jakob J. Metzger,Jennifer Nichols,Eric D. Siggia,Anna-Katerina Hadjantonakis +5 more
TL;DR: The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.
References
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Journal ArticleDOI
The ground state of embryonic stem cell self-renewal
Qi-Long Ying,Jason Wray,Jennifer Nichols,Laura Batlle-Morera,Bradley W. Doble,James R. Woodgett,Philip Cohen,Austin Smith +7 more
TL;DR: It is shown that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells and reveal that ES cells have an innate programme for self-replication that does not require extrinsics instruction.
Journal ArticleDOI
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.
Nathaniel D. Heintzman,Rhona K. Stuart,Gary C. Hon,Yutao Fu,Christina W. Ching,R. David Hawkins,Leah O. Barrera,Sara Van Calcar,Chunxu Qu,Keith A. Ching,Wei Wang,Zhiping Weng,Roland Green,Gregory E. Crawford,Bing Ren +14 more
TL;DR: Insight is given into the connections between chromatin modifications and transcriptional regulatory activity and a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2) is uncovered, providing a new tool for the functional annotation of the human genome.
Journal ArticleDOI
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Warren A. Whyte,David A. Orlando,Denes Hnisz,Brian J. Abraham,Charles Y. Lin,Charles Y. Lin,Michael H. Kagey,Peter B. Rahl,Tong Ihn Lee,Richard A. Young +9 more
TL;DR: In this article, the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state, called super-enhancers, which consist of clusters of enhancers that are densely occupied by the master regulators and Mediator.
Journal ArticleDOI
Super-Enhancers in the Control of Cell Identity and Disease
Denes Hnisz,Brian J. Abraham,Tong Ihn Lee,Ashley Lau,Violaine Saint-André,Alla A. Sigova,Heather A. Hoke,Richard A. Young +7 more
TL;DR: The super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity and play key roles in human cell identity in health and in disease as mentioned in this paper.
Journal ArticleDOI
Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells
Xi Chen,Han Xu,Ping Yuan,Fang Fang,Fang Fang,Mikael Huss,Vinsensius B. Vega,Eleanor Wong,Yuriy L. Orlov,Weiwei Zhang,Weiwei Zhang,Jianming Jiang,Jianming Jiang,Yuin-Han Loh,Yuin-Han Loh,Hock Chuan Yeo,Zhen Xuan Yeo,Vipin Narang,Kunde R Govindarajan,Bernard Leong,Atif Shahab,Yijun Ruan,Guillaume Bourque,Wing-Kin Sung,Neil D. Clarke,Chia-Lin Wei,Huck-Hui Ng,Huck-Hui Ng +27 more
TL;DR: This study uses chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing to map the locations of TF-binding sites and identifies important features of the transcriptional regulatory networks that define ES-cell identity.