Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance
Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance
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DOI：
10.1038/s41467-019-09010-6
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发表时间：
2019-03-05
影响因子：
16.6
通讯作者：
Eisenhoffer, George T.
中科院分区：
文献类型：
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作者：
Brock, Courtney K.;Wallin, Stephen T.;Eisenhoffer, George T.
上皮组织需要去除和替换受损细胞以维持功能屏障。垂死的细胞提供了可以影响周围细胞增殖的指导性线索，但这些信号如何传递给它们的健康邻居以控制组织稳态期间的细胞行为仍然知之甚少。在这里，我们表明，垂死的干细胞促进通讯与邻近的干细胞的半胱天冬酶依赖性生产的Wnt 8a-含有凋亡小体，以推动活上皮细胞的营业额。基底干细胞吞噬凋亡小体，激活Wnt信号传导，并被刺激分裂以维持组织范围的细胞数量。细胞死亡或Wnt信号的抑制消除了凋亡诱导的细胞分裂，而Wnt 8a信号的过表达与诱导的细胞死亡相结合导致干细胞群的扩增。我们的结论是，摄取凋亡小体代表了一种连接死亡和分裂以维持总体干细胞数量和上皮组织稳态的调节机制。
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.