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.

Details

Title
The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells
Author
Kobayashi, Norio 1 ; Okae, Hiroaki 1 ; Hiura, Hitoshi 2 ; Kubota, Naoto 3 ; Kobayashi, Eri H. 1 ; Shibata, Shun 1 ; Oike, Akira 1 ; Hori, Takeshi 4   VIAFID ORCID Logo  ; Kikutake, Chie 3   VIAFID ORCID Logo  ; Hamada, Hirotaka 1   VIAFID ORCID Logo  ; Kaji, Hirokazu 4   VIAFID ORCID Logo  ; Suyama, Mikita 3   VIAFID ORCID Logo  ; Bortolin-Cavaillé, Marie-Line 5 ; Cavaillé, Jérôme 5 ; Arima, Takahiro 1 

1  Tohoku University Graduate School of Medicine, Department of Informative Genetics, Environment and Genome Research Center, Sendai, Japan (GRID:grid.69566.3a) (ISNI:0000 0001 2248 6943) 
2  Tokyo University of Agriculture, Department of Bioscience, Faculty of Life Science, Tokyo, Japan (GRID:grid.410772.7) (ISNI:0000 0001 0807 3368) 
3  Kyushu University, Division of Bioinformatics, Medical Institute of Bioregulation, Fukuoka, Japan (GRID:grid.177174.3) (ISNI:0000 0001 2242 4849) 
4  Tokyo Medical and Dental University, Department of Biomechanics, Institute of Biomaterials and Bioengineering, Tokyo, Japan (GRID:grid.265073.5) (ISNI:0000 0001 1014 9130) 
5  University of Toulouse, CNRS, UPS, Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Intégrative (CBI), Toulouse, France (GRID:grid.15781.3a) (ISNI:0000 0001 0723 035X) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-30775-w
ProQuest document ID
2672493031
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.