RRC ID 48891
Author Yagi M, Kishigami S, Tanaka A, Semi K, Mizutani E, Wakayama S, Wakayama T, Yamamoto T, Yamada Y.
Title Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Journal Nature
Abstract Inhibitors of Mek1/2 and Gsk3β, known as 2i, enhance the derivation of embryonic stem (ES) cells and promote ground-state pluripotency in rodents. Here we show that the derivation of female mouse ES cells in the presence of 2i and leukaemia inhibitory factor (2i/L ES cells) results in a widespread loss of DNA methylation, including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, early-passage 2i/L ES cells efficiently differentiate into somatic cells, and this process requires genome-wide de novo DNA methylation. However, the majority of imprinting control regions (ICRs) remain unmethylated in 2i/L-ES-cell-derived differentiated cells. Consistently, 2i/L ES cells exhibit impaired autonomous embryonic and placental development by tetraploid embryo complementation or nuclear transplantation. We identified the derivation conditions of female ES cells that display 2i/L-ES-cell-like transcriptional signatures while preserving gamete-derived DNA methylation and autonomous developmental potential. Upon prolonged culture, however, female ES cells exhibited ICR demethylation regardless of culture conditions. Our results provide insights into the derivation of female ES cells reminiscent of the inner cell mass of preimplantation embryos.
Volume 548(7666)
Pages 224-227
Published 2017-8-10
DOI 10.1038/nature23286
PII nature23286
PMID 28746308
MeSH Animals Cell Differentiation / drug effects Cell Differentiation / genetics* DNA Methylation / drug effects DNA Methylation / genetics* Embryonic Stem Cells / cytology* Embryonic Stem Cells / drug effects Female Genomic Imprinting / drug effects Glycogen Synthase Kinase 3 beta / antagonists & inhibitors Leukemia Inhibitory Factor / pharmacology MAP Kinase Kinase 1 / antagonists & inhibitors MAP Kinase Kinase 2 / antagonists & inhibitors Mice Mice, Inbred C57BL
IF 42.779
Times Cited 67
Mice RBRC00209
Human and Animal Cells Dnmt1-/-Dnmt3a-/-Dnmt3b-/- ES (clone19)(AES0146)