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

Joanna J. Gell; Wanlu Liu; Enrique Sosa; Alex Chialastri; Grace Hancock; Yu Tao; Sissy E. Wamaitha; Grace Bower; Siddharth S. Dey; Amander T. Clark

Stem Cell Reports (Mar 2020)

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

Joanna J. Gell,
Wanlu Liu,
Enrique Sosa,
Alex Chialastri,
Grace Hancock,
Yu Tao,
Sissy E. Wamaitha,
Grace Bower,
Siddharth S. Dey,
Amander T. Clark

Affiliations

Joanna J. Gell: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA; David Geffen School of Medicine, Department of Pediatrics, Division of Hematology-Oncology, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA
Wanlu Liu: Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou 310058, P. R. China
Enrique Sosa: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA
Alex Chialastri: Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA; Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Grace Hancock: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA
Yu Tao: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA
Sissy E. Wamaitha: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA
Grace Bower: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA
Siddharth S. Dey: Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA; Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Amander T. Clark: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA; Corresponding author

Journal volume & issue: Vol. 14, no. 3
pp. 433 – 446

Abstract

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Summary: 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. : In the article, Clark and colleagues describe a 2D culture system that supports the expansion of human primordial germ cell-like cells (hPGCLCs) differentiated from human pluripotent stem cells. The cultured hPGCLCs maintains germline identity, while undergoing proliferation and initiating DNA demethylation. Creating a culture system that supports hPGCLCs provides new opportunities to promote the differentiation of hPGCLCs into gametes. Keywords: human, primordial germ cells, primordial germ cell-like cells

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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