An Extended Culture System that Supports Human Primordial Germ Cell-like Cell Survival and Initiation of DNA Methylation Erasure.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, MA] : Cell Press, c 2013-
    • Subject Terms:
      DNA Methylation*/genetics; Cell Culture Techniques/*methods ; Germ Cells/*cytology; Cell Proliferation ; Cell Self Renewal ; Cell Survival ; Cells, Cultured ; Chromatin Assembly and Disassembly ; DNA Demethylation ; Histones/metabolism ; Humans ; Transcription, Genetic ; Transcriptome/genetics
    • Abstract:
      The development of an in vitro system in which human primordial germ cell-like cells (hPGCLCs) are generated from human pluripotent stem cells (hPSCs) has been invaluable to further our understanding of human primordial germ cell (hPGC) specification. However, the means to evaluate the next fundamental steps in germ cell development have not been well established. In this study we describe a two dimensional extended culture system that promotes proliferation of specified hPGCLCs, without reversion to a pluripotent state. We demonstrate that hPGCLCs in extended culture undergo partial epigenetic reprogramming, mirroring events described in hPGCs in vivo, including a genome-wide reduction in DNA methylation and maintenance of depleted H3K9me2. This extended culture system provides a new approach for expanding the number of hPGCLCs for downstream technologies, including transplantation, molecular screening, or possibly the differentiation of hPGCLCs into gametes by in vitro gametogenesis.
      (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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    • Grant Information:
      R01 HD058047 United States HD NICHD NIH HHS; R01 HD079546 United States HD NICHD NIH HHS; R24 HD000836 United States HD NICHD NIH HHS
    • Contributed Indexing:
      Keywords: human; primordial germ cell-like cells; primordial germ cells
    • Accession Number:
      0 (Histones)
    • Publication Date:
      Date Created: 20200216 Date Completed: 20210204 Latest Revision: 20240328
    • Publication Date:
      20240329
    • Accession Number:
      PMC7066331
    • Accession Number:
      10.1016/j.stemcr.2020.01.009
    • Accession Number:
      32059791