Characterisation of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming

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Title: Characterisation of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming
Author(s): Eguizabal, C
Herrera, L
De Onate, L
Montserrat, N
Hajkova, P
Izpisua Belmonte, JC
Item Type: Journal Article
Abstract: 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.
Publication Date: 30-Jun-2016
Date of Acceptance: 29-Apr-2016
URI: http://hdl.handle.net/10044/1/34388
DOI: https://dx.doi.org/10.1002/stem.2422
ISSN: 1066-5099
Publisher: Wiley
Start Page: 2418
End Page: 2428
Journal / Book Title: Stem Cells
Volume: 34
Issue: 9
Copyright Statement: This is the peer reviewed version of the following article: Eguizabal, C., Herrera, L., De Oñate, L., Montserrat, N., Hajkova, P. and Izpisua Belmonte, J. C. (2016), Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming. STEM CELLS, which has been published in final form at https://dx.doi.org/10.1002/stem.2422. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Sponsor/Funder: Commission of the European Communities
EMBO
Commission of the European Communities
Funder's Grant Number: 257082
EMBO YIP
648879
Keywords: Epigenetic
Human primordial germ cells
Reprograming
Immunology
06 Biological Sciences
10 Technology
11 Medical And Health Sciences
Publication Status: Published
Embargo Date: 2017-06-30
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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