后肠类器官支持的具有增强发育能力的人类生殖细胞命运的特化。
Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids.
作者信息
Alves-Lopes João Pedro, Wong Frederick C K, Tang Walfred W C, Gruhn Wolfram H, Ramakrishna Navin B, Jowett Geraldine M, Jahnukainen Kirsi, Surani M Azim
机构信息
Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, J9:30, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Visionsgatan 4, Solna, 17164 Stockholm, Sweden.
Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
出版信息
Cell Rep. 2023 Jan 31;42(1):111907. doi: 10.1016/j.celrep.2022.111907. Epub 2023 Jan 5.
Human primordial germ cells (hPGCs), the precursors of sperm and eggs, are specified during weeks 2-3 after fertilization. Few studies on ex vivo and in vitro cultured human embryos reported plausible hPGCs on embryonic day (E) 12-13 and in an E16-17 gastrulating embryo. In vitro, hPGC-like cells (hPGCLCs) can be specified from the intermediary pluripotent stage or peri-gastrulation precursors. Here, we explore the broad spectrum of hPGCLC precursors and how different precursors impact hPGCLC development. We show that resetting precursors can give rise to hPGCLCs (rhPGCLCs) in response to BMP. Strikingly, rhPGCLCs co-cultured with human hindgut organoids progress at a pace reminiscent of in vivo hPGC development, unlike those derived from peri-gastrulation precursors. Moreover, rhPGCLC specification depends on both EOMES and TBXT, not just on EOMES as for peri-gastrulation hPGCLCs. Importantly, our study provides the foundation for developing efficient in vitro models of human gametogenesis.
人类原始生殖细胞（hPGCs）是精子和卵子的前体，在受精后第2至3周形成。关于体外和体外培养的人类胚胎的研究很少报告在胚胎第12至13天以及第16至17天的原肠胚中存在似是而非的hPGCs。在体外，hPGC样细胞（hPGCLCs）可以从中等多能阶段或原肠胚形成前期的前体中产生。在这里，我们探索了hPGCLC前体的广泛谱系，以及不同前体如何影响hPGCLC的发育。我们表明，重编程前体在BMP的作用下可以产生hPGCLCs（rhPGCLCs）。令人惊讶的是，与人类后肠类器官共培养的rhPGCLCs的发育速度让人想起体内hPGC的发育，这与源自原肠胚形成前期前体的hPGCLCs不同。此外，rhPGCLC的形成不仅依赖于EOMES，还依赖于TBXT，而原肠胚形成前期的hPGCLCs只依赖于EOMES。重要的是，我们的研究为开发高效的人类配子发生体外模型奠定了基础。
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