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

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An Extended Culture System that Supports Human Primordial Germ Cell-like Cell Survival and Initiation of DNA Methylation Erasure.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-02-13 , DOI: 10.1016/j.stemcr.2020.01.009
Joanna J Gell ₁ , Wanlu Liu ₂ , Enrique Sosa ₃ , Alex Chialastri ₄ , Grace Hancock ₅ , Yu Tao ₃ , Sissy E Wamaitha ₃ , Grace Bower ₆ , Siddharth S Dey ₇ , Amander T Clark ₈

Affiliation

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.
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou 310058, P. R. China.
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.
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.
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.
Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
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.
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.

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.

中文翻译：

支持人类原始生殖细胞样细胞存活和DNA甲基化清除起始的扩展培养系统。

从人多能干细胞（hPSC）生成人原始生殖细胞样细胞（hPGCLC）的体外系统的开发对于进一步了解人类原始生殖细胞（hPGC）规范具有重要的价值。但是，尚未很好地建立评估生殖细胞发育中下一步基本步骤的方法。在这项研究中，我们描述了二维扩展培养系统，该系统可促进特定hPGCLC的增殖，而不会回复到多能状态。我们证明在扩展的文化hPGCLCs经历部分表观遗传重编程，镜像事件在hPGC体内描述，包括全基因组DNA甲基化减少和维持H3K9me2耗尽。这种扩展的培养系统提供了一种新的方法，用于扩展用于下游技术的hPGCLC的数量，包括移植，分子筛选或可能通过体外配子发生将hPGCLC分化为配子。

更新日期：2020-02-13

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