加拿大渥太华大学Armen Saghatelyan团队发现，神经干细胞的静息和激活动态在稳态和再生条件下受到其子代反馈输入的调控。相关论文于2025年2月6日在线发表在《细胞—干细胞》杂志上。

研究人员在小鼠成年亚脑室神经干细胞（NSC）微环境中绘制了NSC功能反应的精确时空图谱，这些反应是由多个微环境细胞诱导的，并使用机器学习预测了NSC与特定微环境细胞类型的相互作用。研究人员揭示了一种反馈机制，其中NSC的增殖状态受到瞬时扩增细胞（TAP）——它们快速分裂的子代——的直接抑制。

NSC的过程包裹在TAP周围，并在接触点显示出钙离子（Ca²⁺）活性的热点，这一过程由ephrin（Efn）信号介导。Efn信号的调节或TAP的消除改变了NSC的Ca²⁺特征，导致其激活。体内光遗传学调节Ca²⁺动态抑制了NSC的激活并防止了微环境的补充。因此，TAP到NSC的反馈信号调控干细胞的静息和激活，为维持终身干细胞库提供了一种机制。

附：英文原文

Title: Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions

Author: Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan

Issue&Volume: 2025-02-06

Abstract: Life-long maintenance of stem cells implies that feedback mechanisms from the niche regulate their quiescence/activation dynamics. Here, in the mouse adult subventricular neural stem cell (NSC) niche, we charted a precise spatiotemporal map of functional responses in NSCs induced by multiple niche cells and used machine learning to predict NSC interactions with specific niche cell types. We revealed a feedback mechanism whereby the NSC proliferative state is directly repressed by transient amplifying cells (TAPs), their rapidly dividing progeny. NSC processes wrap around TAPs and display hotspots of Ca2+ activity at their points of contact, mediated by ephrin (Efn) signaling. The modulation of Efn signaling or TAP ablation altered the Ca2+ signature of NSCs, leading to their activation. In vivo optogenetic modulation of Ca2+ dynamics abrogated NSC activation and prevented niche replenishment. Thus, TAP-to-NSC feedback signaling controls stem cell quiescence and activation, providing a mechanism to maintain stem cell pools throughout life.

DOI: 10.1016/j.stem.2025.01.001

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00001-3