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 - Funding Information:
We would like to thank Dr. K. Nakayama, Dr. R. Funayama, Ms. M. Kikuchi, and Ms. A. Kitamura (Tohoku University) for technical assistance and Dr. RM. John (Cardiff University) for support and valuable suggestions. We thank Dr. H. Akutsu and Dr. A. Umezawa (National Center for Child Health and Development) for providing SEES1 and SEES4 hES cells. We also thank the Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. This work was supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI) Grant 19K16135 and 22K15117 and the Sasakawa Scientific Research Grant from The Japan Science Society (to N. Kobayashi), and the Research Center for Biomedical Engineering (to H.K.), and La Ligue Régionale contre le Cancer (to J.C.), and KAKENHI Grant 19H05757 and 21H03072, Japan Agency for Medical Research and Development (AMED) Grant JP18bm0704021, and the Naito Foundation (to H.O.), and the Core Research for Evolutional Science and Technology from AMED Grants JP17gm0510011 and JP19gm1310001, KAKENHI Grant 17H04335 and 21H04834, Smoking Research Foundation, the Mitsubishi Foundation, and Takeda Science Foundation (to T.A.).
Funding Information:
We would like to thank Dr. K. Nakayama, Dr. R. Funayama, Ms. M. Kikuchi, and Ms. A. Kitamura (Tohoku University) for technical assistance and Dr. RM. John (Cardiff University) for support and valuable suggestions. We thank Dr. H. Akutsu and Dr. A. Umezawa (National Center for Child Health and Development) for providing SEES1 and SEES4 hES cells. We also thank the Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. This work was supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI) Grant 19K16135 and 22K15117 and the Sasakawa Scientific Research Grant from The Japan Science Society (to N. Kobayashi), and the Research Center for Biomedical Engineering (to H.K.), and La Ligue Régionale contre le Cancer (to J.C.), and KAKENHI Grant 19H05757 and 21H03072, Japan Agency for Medical Research and Development (AMED) Grant JP18bm0704021, and the Naito Foundation (to H.O.), and the Core Research for Evolutional Science and Technology from AMED Grants JP17gm0510011 and JP19gm1310001, KAKENHI Grant 17H04335 and 21H04834, Smoking Research Foundation, the Mitsubishi Foundation, and Takeda Science Foundation (to T.A.).
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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UR - http://www.scopus.com/inward/citedby.url?scp=85131139855&partnerID=8YFLogxK
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 -