期刊
STEM CELLS
卷 34, 期 9, 页码 2418-2428出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.2422
关键词
Epigenetic; Reprograming; Human primordial germ cells
资金
- Fundacio Privada La Marato de TV3 [121430/31/32]
- Spanish Ministry of Economy and Competitiveness [SAF2014-59778]
- Commission for Universities and Research of the Department of Innovation, Universities, Enterprise of the Generalitat de Catalunya [2014 SGR 1442]
- Networking Center of Biomedical Research in Bioengineering, Biomaterials and Nanomedicine (CIBER)
- G. Harold and Leila Y. Mathers Charitable Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- The Moxie Foundation
- [BIOEF12/018]
- [StG-2014-640525 REGMAMKID]
- [RyC 2014-16242]
- MRC [MC_U120092689] Funding Source: UKRI
- Medical Research Council [MC_U120092689] Funding Source: researchfish
Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads.
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