We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells.
- Authors
Kobayashi, Norio; Okae, Hiroaki; Hiura, Hitoshi; Kubota, Naoto; Kobayashi, Eri H.; Shibata, Shun; Oike, Akira; Hori, Takeshi; Kikutake, Chie; Hamada, Hirotaka; Kaji, Hirokazu; Suyama, Mikita; Bortolin-Cavaillé, Marie-Line; Cavaillé, Jérôme; Arima, Takahiro
- 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. Little is known about the epigenetic mechanisms of the first cell fate commitment in humans. Here, the authors show that activation of the miRNA cluster C19MC confers differentiation potential into trophoblast lineages on human embryonic stem cells.
- Subjects
TROPHOBLAST; PLURIPOTENT stem cells; HUMAN stem cells; HUMAN embryonic stem cells; CELL determination; CELL differentiation; MICRORNA
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30775-w