Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7045, Cincinnati, OH, 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Avenue, Suite E-870, Cincinnati, OH, 45267, USA.
Nat Commun. 2018 Oct 30;9(1):4519. doi: 10.1038/s41467-018-06996-3.
Androgens responsible for male sexual differentiation in utero are produced by Leydig cells in the fetal testicular interstitium. Leydig cells rarely proliferate and, hence, rely on constant differentiation of interstitial progenitors to increase their number during fetal development. The cellular origins of fetal Leydig progenitors and how they are maintained remain largely unknown. Here we show that Notch-active, Nestin-positive perivascular cells in the fetal testis are a multipotent progenitor population, giving rise to Leydig cells, pericytes, and smooth muscle cells. When vasculature is disrupted, perivascular progenitor cells fail to be maintained and excessive Leydig cell differentiation occurs, demonstrating that blood vessels are a critical component of the niche that maintains interstitial progenitor cells. Additionally, our data strongly supports a model in which fetal Leydig cell differentiation occurs by at least two different means, with each having unique progenitor origins and distinct requirements for Notch signaling to maintain the progenitor population.
在子宫内负责男性性分化的雄激素是由胎儿睾丸间质中的莱迪希细胞产生的。莱迪希细胞很少增殖，因此，在胎儿发育过程中，它们依赖于间质祖细胞的持续分化来增加数量。胎儿莱迪希祖细胞的细胞起源以及它们如何被维持在很大程度上仍然未知。在这里，我们表明，胎儿睾丸中的 Notch 活性、巢蛋白阳性的血管周细胞是多能祖细胞群，可分化为莱迪希细胞、周细胞和平滑肌细胞。当血管受到破坏时，血管周祖细胞不能被维持，并且过度的莱迪希细胞分化发生，这表明血管是维持间质祖细胞的小生境的关键组成部分。此外，我们的数据强烈支持这样一种模型，即胎儿莱迪希细胞分化至少通过两种不同的方式发生，每种方式都有独特的祖细胞起源，并对 Notch 信号有不同的要求来维持祖细胞群体。
