Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming.
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. Stem Cells 2016;34:2418-2428.
Cell Therapy and Stem Cell Group, Basque Center for Transfusion and Human Tissues, Galdakao, Spain.
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Eguizabal
Cell Therapy and Stem Cell Group, Basque Center for Transfusion and Human Tissues, Galdakao, Spain.
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Herrera
Pluripotent Stem Cells and Activation of Endogenous Tissue Programs for Organ Regeneration (PR Lab), Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.
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De Oñate
Pluripotent Stem Cells and Activation of Endogenous Tissue Programs for Organ Regeneration (PR Lab), Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.|CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
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Montserrat
Reprogramming and Chromatin Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.|Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN.
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Hajkova
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA. belmonte@salk.edu.
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Izpisua Belmonte
D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D006066:Gonads / Q000166:cytology*; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000378:metabolism; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; C087042:PRDM1 protein, human; D056466:Histone Demethylases; C495195:KDM1A protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D008239:Lysine
Epigenetic; Human primordial germ cells; Reprograming