Dynamic chromatin remodeling mediated by polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells

Item Type:	Article
Title:	Dynamic chromatin remodeling mediated by polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells
Creators Name:	Xie, R. and Everett, L.J. and Lim, H.W. and Patel, N.A. and Schug, J. and Kroon, E. and Kelly, O.G. and Wang, A. and D'Amour, K.A. and Robins, A.J. and Won, K.J. and Kaestner, K.H. and Sander, M.
Abstract:	Embryonic development is characterized by dynamic changes in gene expression, yet the role of chromatin remodeling in these cellular transitions remains elusive. To address this question, we profiled the transcriptome and select chromatin modifications at defined stages during pancreatic endocrine differentiation of human embryonic stem cells. We identify removal of Polycomb group (PcG)-mediated repression on stage-specific genes as a key mechanism for the induction of developmental regulators. Furthermore, we discover that silencing of transitory genes during lineage progression associates with reinstatement of PcG-dependent repression. Significantly, in vivo- but not in vitro-differentiated endocrine cells exhibit close similarity to primary human islets in regard to transcriptome and chromatin structure. We further demonstrate that endocrine cells produced in vitro do not fully eliminate PcG-mediated repression on endocrine-specific genes, probably contributing to their malfunction. These studies reveal dynamic chromatin remodeling during developmental lineage progression and identify possible strategies for improving cell differentiation in culture.
Keywords:	Cell Differentiation, Chromatin Assembly and Disassembly, Embryonic Stem Cells, Endocrine Cells, Endoderm, Pancreas, Polycomb-Group Proteins, Animals, Mice
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Cell Press
Volume:	12
Number:	2
Page Range:	224-37
Date:	7 February 2013
Official Publication:	https://doi.org/10.1016/j.stem.2012.11.023
PubMed:	View item in PubMed

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