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Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells

Item Type:Article
Title:Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells
Creators Name:Yang, M. and Yu, H. and Yu, X. and Liang, S. and Hu, Y. and Luo, Y. and Izsvák, Z. and Sun, C. and Wang, J.
Abstract:Totipotent cells have more robust developmental potency than any other cell types, giving rise to both embryonic and extraembryonic tissues. Stable totipotent cell cultures and deciphering the principles of totipotency regulation would be invaluable to understand cell plasticity and lineage segregation in early development. Our approach of remodeling the pericentromeric heterochromatin and re-establishing the totipotency-specific broad H3K4me3 domains promotes the pluri-to-totipotency transition. Our protocol establishes a closer match of mouse 2-cell (2C) embryos than any other 2C-like cells. These totipotent-like stem cells (TLSCs) are stable in culture and possess unique molecular features of the mouse 2C embryo. Functionally, TLSCs are competent for germline transmission and give rise to both embryonic and extraembryonic lineages at high frequency. Therefore, TLSCs represent a highly valuable cell type for studies of totipotency and embryology.
Keywords:Totipotency, 2C-Like Cells, MERVL, Dot1l, Kdm5b, Pericentromeric Heterochromatin, Chromocenter, Broad H3K4me3 Domains, Blastoid, Animals, Mice
Source:Cell Stem Cell
ISSN:1934-5909
Publisher:Cell Press
Volume:29
Number:3
Page Range:400-418.e13
Date:3 March 2022
Official Publication:https://doi.org/10.1016/j.stem.2022.01.010
PubMed:View item in PubMed

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