Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Genetics and Epigenetics Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Nat Commun. 2019 Mar 5;10(1):1044. doi: 10.1038/s41467-019-09010-6.
Epithelial tissues require the removal and replacement of damaged cells to sustain a functional barrier. Dying cells provide instructive cues that can influence surrounding cells to proliferate, but how these signals are transmitted to their healthy neighbors to control cellular behaviors during tissue homeostasis remains poorly understood. Here we show that dying stem cells facilitate communication with adjacent stem cells by caspase-dependent production of Wnt8a-containing apoptotic bodies to drive cellular turnover in living epithelia. Basal stem cells engulf apoptotic bodies, activate Wnt signaling, and are stimulated to divide to maintain tissue-wide cell numbers. Inhibition of either cell death or Wnt signaling eliminated the apoptosis-induced cell division, while overexpression of Wnt8a signaling combined with induced cell death led to an expansion of the stem cell population. We conclude that ingestion of apoptotic bodies represents a regulatory mechanism linking death and division to maintain overall stem cell numbers and epithelial tissue homeostasis.
上皮组织需要去除和替换受损细胞以维持功能屏障。垂死的细胞提供了有指导意义的线索，可以影响周围的细胞增殖，但这些信号如何传递给它们健康的邻居，以控制组织内稳态期间的细胞行为，目前还知之甚少。在这里，我们表明，垂死的干细胞通过 caspase 依赖性产生包含 Wnt8a 的凋亡小体来促进与相邻干细胞的通讯，以驱动活上皮细胞的细胞周转。基底干细胞吞噬凋亡小体，激活 Wnt 信号，并受到刺激进行分裂以维持组织范围内的细胞数量。抑制细胞死亡或 Wnt 信号均消除了凋亡诱导的细胞分裂，而 Wnt8a 信号的过表达与诱导的细胞死亡相结合导致干细胞群体的扩张。我们得出结论，吞噬凋亡小体代表了一种调节机制，将死亡和分裂联系起来，以维持整体干细胞数量和上皮组织内稳态。
