Warder Bailey N, Nelson Kara A, Sui Justin, Anllo Lauren, DiNardo Stephen
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
bioRxiv. 2024 Aug 7:2023.09.08.556877. doi: 10.1101/2023.09.08.556877.
Stem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed, and how morphology impacts function. To address this, we leverage the gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad, and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and Non-muscle Myosin II (MyoII) towards neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells, and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.
干细胞通常依赖于来自微环境的信号，在许多组织中，微环境具有精确的形态。目前仍不清楚的是微环境是如何形成的，以及形态如何影响功能。为了解决这个问题，我们利用性腺微环境，它具有遗传易处理性和活体成像功能。我们之前已经展示了决定微环境细胞迁移到性腺内适当位置的机制，以及对微环境功能的最终影响。在这里，我们表明，一旦定位，微环境细胞会强烈地将丝状肌动蛋白（F-肌动蛋白）和非肌肉肌球蛋白II（肌球蛋白II）向相邻的生殖细胞极化。沿着微环境周边的肌动球蛋白张力产生高度可重复的平滑轮廓。没有收缩性，微环境就会变形，并且在调节生殖系干细胞行为的能力上表现出缺陷。我们还表明，生殖细胞有助于在微环境细胞内使肌球蛋白II极化，并且微环境形态发生和功能需要外部输入。我们的工作揭示了一种反馈机制，即干细胞塑造指导其行为的微环境。
