TY - JOUR
T1 - The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells
AU - Kobayashi, Norio
AU - Okae, Hiroaki
AU - Hiura, Hitoshi
AU - Kubota, Naoto
AU - Kobayashi, Eri H.
AU - Shibata, Shun
AU - Oike, Akira
AU - Hori, Takeshi
AU - Kikutake, Chie
AU - Hamada, Hirotaka
AU - Kaji, Hirokazu
AU - Suyama, Mikita
AU - Bortolin-Cavaillé, Marie Line
AU - Cavaillé, Jérôme
AU - Arima, Takahiro
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30775-w
DO - 10.1038/s41467-022-30775-w
M3 - Article
C2 - 35654791
AN - SCOPUS:85131139855
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3071
ER -