肠道干细胞通过自我更新分裂来转换多能性

肠道干细胞通过自我更新分裂来转换多能性

作者： 小柯机器人 发布时间：2026/8/3 16:20:09

本期文章：《自然》：Online/在线发表

肠道干细胞通过自我更新分裂来转换多能性，这一成果由华中科技大学郭峥团队经过不懈努力而取得。相关论文于2026年7月29日发表在《自然》杂志上。

本研究表明，ISCs本质上通过表观遗传机制来计数自我更新分裂，以控制多能性转换。在每一个不对称分裂产生一个肠内分泌母细胞（EMC；它对称分裂产生一对EECs）之后，ISCs精确地执行8次分裂产生ECs，然后在第9次分裂时切换回EMC生产。这种计数是由拮抗组蛋白修饰驱动的：Trithorax组（TrxG）依赖的活性标记（H3K4me3和H3K36me3）逐渐下降，而Polycomb组（PcG）依赖的抑制标记（H3K27me3）在连续的分裂中积累，在阈值处触发命运转换。

细胞分裂计数可通过调节TrxG和PcG活性来调节，但可抵抗急性损伤。至关重要的是，EMC衍生的瞬态Notch信号在ISCs中建立主动标记以启动计数，将每个EMC生产指定为周期的起点。他们的工作确定了一种基于组蛋白修饰的分裂计数器，该计数器可以编程干细胞的发育保真度，这对工程化组织生长和分化障碍治疗具有重要意义。

研究人员表示，多能干细胞通过按特定比例产生不同的子细胞类型来维持组织稳态，但它们如何在重复分裂中协调特定类型的比例仍然未知。果蝇肠道干细胞（ISCs）在产生肠内分泌细胞（EECs）和肠细胞（ECs）之间切换，尽管组织快速更替，但仍保持恒定的EEC:EC比率。

附：英文原文

Title: Intestinal stem cells count self-renewal divisions to switch multipotency

Author: Tong, Dong, Li, Anqi, Jiang, Quanquan, Yuan, Qili, Liu, Xiaozhao, He, Ximiao, Liang, Jiejunyi, Han, Yunyun, Guo, Zheng

Issue&Volume: 2026-07-29

Abstract: Multipotent stem cells maintain tissue homeostasis by producing distinct daughter cell types in defined proportions1,2, but how they coordinate type-specific ratios during repeated divisions remains unknown. Drosophila intestinal stem cells (ISCs) switch between producing enteroendocrine cells (EECs) and enterocytes (ECs)3,4, yet maintain a constant EEC:EC ratio despite rapid tissue turnover5,6,7. Here we show that ISCs intrinsically count self-renewal divisions through an epigenetic mechanism to control multipotency switching. After each asymmetrical division producing an enteroendocrine mother cell (EMC; which divides symmetrically to produce a pair of EECs), ISCs execute precisely eight divisions that generate ECs, before switching back to EMC production at the ninth division. This counting is driven by antagonistic histone modifications: Trithorax group (TrxG)-dependent active marks (H3K4me3 and H3K36me3) progressively decline, whereas Polycomb group (PcG)-dependent repressive marks (H3K27me3) accumulate over successive divisions, triggering fate switching at a threshold. The division count is tunable by modulating TrxG and PcG activities, but withstands acute injury. Crucially, EMC-derived transient Notch signalling establishes active marks in ISCs to initiate the count, designating each EMC production as the cycle’s start point. Our work identifies a histone-modification-based division counter that programs developmental fidelity in stem cells, with implications for engineered tissue growth and differentiation disorder therapies.

DOI: 10.1038/s41586-026-10814-y

Source: https://www.nature.com/articles/s41586-026-10814-y

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