RRC ID 72355
Author Kobayashi N, Okae H, Hiura H, Kubota N, Kobayashi EH, Shibata S, Oike A, Hori T, Kikutake C, Hamada H, Kaji H, Suyama M, Bortolin-Cavaillé ML, Cavaillé J, Arima T.
Title The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells.
Journal Nat Commun
Abstract The first cell fate commitment during mammalian development is the specification of the inner cell mass and trophectoderm. This irreversible cell fate commitment should be epigenetically regulated, but the precise mechanism is largely unknown in humans. Here, we show that naïve human embryonic stem (hES) cells can transdifferentiate into trophoblast stem (hTS) cells, but primed hES cells cannot. Our transcriptome and methylome analyses reveal that a primate-specific miRNA cluster on chromosome 19 (C19MC) is active in naïve hES cells but epigenetically silenced in primed ones. Moreover, genome and epigenome editing using CRISPR/Cas systems demonstrate that C19MC is essential for hTS cell maintenance and C19MC-reactivated primed hES cells can give rise to hTS cells. Thus, we reveal that C19MC activation confers differentiation potential into trophoblast lineages on hES cells. Our findings are fundamental to understanding the epigenetic regulation of human early development and pluripotency.
Volume 13(1)
Pages 3071
Published 2022-6-2
DOI 10.1038/s41467-022-30775-w
PII 10.1038/s41467-022-30775-w
PMID 35654791
PMC PMC9163035
MeSH Animals Cell Differentiation / genetics Epigenesis, Genetic Humans Mammals MicroRNAs* / genetics Pluripotent Stem Cells* Trophoblasts
DNA material CS-CA-MCS (RDB05963) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)