The division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. Here, we developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analyzing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT can provide novel insights into stem cell behavior. Further, we use single-cell RNA sequencing (scRNA-seq) of iCOUNT-labeled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify functionally relevant molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair.

单个干细胞的分裂潜力和连续几轮增殖的分子后果在很大程度上仍然未知。在这里，我们开发了一种诱导型细胞分裂计数器 (iCOUNT)，它可以在体外和体内报告人和小鼠组织中的细胞分裂事件. 分析发育中和成人大脑中神经干/祖细胞 (NSPC) 的细胞分裂历史，我们表明 iCOUNT 可以为干细胞行为提供新的见解。此外，我们使用 iCOUNT 标记的 NSPC 及其后代的单细胞 RNA 测序 (scRNA-seq) 来自发育中的小鼠皮层和前脑区域化的人类类器官，以确定小鼠和人类细胞之间通常调节的功能相关分子途径，具体取决于关于单个细胞分裂历史。因此，我们开发了一种工具来表征干细胞重复细胞分裂的分子后果，从而可以分析组织形成、体内平衡和修复的细胞原理。