The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Development. 2023 Sep 1;150(17). doi: 10.1242/dev.201790. Epub 2023 Sep 11.
Primordial germ cells (PGCs) are the early embryonic precursors of gametes - sperm and egg cells. PGC-like cells (PGCLCs) can currently be derived in vitro from pluripotent cells exposed to signalling cocktails and aggregated into large embryonic bodies, but these do not recapitulate the native embryonic environment during PGC formation. Here, we show that mouse gastruloids, a three-dimensional in vitro model of gastrulation, contain a population of gastruloid-derived PGCLCs (Gld-PGCLCs) that resemble early PGCs in vivo. Importantly, the conserved organisation of mouse gastruloids leads to coordinated spatial and temporal localisation of Gld-PGCLCs relative to surrounding somatic cells, even in the absence of specific exogenous PGC-specific signalling or extra-embryonic tissues. In gastruloids, self-organised interactions between cells and tissues, including the endodermal epithelium, enables the specification and subsequent maturation of a pool of Gld-PGCLCs. As such, mouse gastruloids represent a new source of PGCLCs in vitro and, owing to their inherent co-development, serve as a novel model to study the dynamics of PGC development within integrated tissue environments.
原始生殖细胞（PGCs）是配子——精子和卵子的早期胚胎前体。目前，可以通过向多能细胞暴露于信号鸡尾酒并聚集到大型胚胎体中来体外衍生出类原始生殖细胞（PGCLC），但这些细胞不能在 PGC 形成过程中再现内源性胚胎环境。在这里，我们表明，鼠胚状体，即胚层形成的三维体外模型，含有一群胚状体衍生的 PGCLC（Gld-PGCLCs），这些细胞在体内类似于早期 PGC。重要的是，保守的鼠胚状体组织导致 Gld-PGCLCs 相对于周围体细胞的协调空间和时间定位，即使在没有特定的外源性 PGC 特异性信号或胚胎外组织的情况下也是如此。在胚状体中，细胞和组织之间的自组织相互作用，包括内胚层上皮，使 Gld-PGCLCs 池的特化和随后的成熟成为可能。因此，鼠胚状体代表了体外 PGCLC 的新来源，并且由于其固有的共同发育，它们可用作研究集成组织环境中 PGC 发育动态的新型模型。
