Transiently "Undead" Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut.

Transiently "Undead" Enterocytes Mediate Homeostatic Tissue Turnover in the Adult Drosophila Midgut.
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DOI:
10.1016/j.celrep.2020.108408
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发表时间:
2020-11-24
期刊:
影响因子:
8.8
通讯作者:
Bergmann A
Bergmann A
中科院分区:
生物学1区
文献类型:
--
作者:
Amcheslavsky A;Lindblad JL;Bergmann A

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我们揭示了令人惊讶的相似之处,稳态细胞营业额在成年果蝇中肠和''不死'' adoptosis-induced代偿性增殖(AiP)在成虫盘。在不死的AiP期间,永生化细胞发出AiP信号,允许其分析。不死的AiP的关键是Myo 1D依赖性的启动子胱天蛋白酶Dronc定位到质膜。在这里,我们发现Myo 1D在成熟的肠上皮细胞(EC)中起作用,以控制肠干细胞(ISCs)的有丝分裂活性。在Myo 1D突变体中肠中,AiP(ROS生成,血细胞募集和JNK信号传导)中涉及的许多信号传导事件受到影响。重要的是,与AiP类似,Myo 1D是Dronc在EC中的膜定位所必需的。我们提出,注定要死的EC通过Dronc的Myo 1D依赖性膜定位暂时进入一种未死样状态,这使它们能够产生ISC活性及其替换的信号。暂时“不死”细胞的概念可能与苍蝇和哺乳动物中的其他干细胞模型有关。Amcheslavsky等人揭示了一种机制,根据该机制,凋亡细胞以Myo 1D依赖性方式通过Dronc的膜定位进入“不死”样状态,从而短暂维持生存。这种短暂的“不死”样状态使凋亡细胞在短时间内产生干细胞有丝分裂活动的信号。
We reveal surprising similarities between homeostatic cell turnover in adult Drosophila midguts and ‘‘undead’’ apoptosis-induced compensatory proliferation (AiP) in imaginal discs. During undead AiP, immortalized cells signal for AiP, allowing its analysis. Critical for undead AiP is the Myo1D-dependent localization of the initiator caspase Dronc to the plasma membrane. Here, we show that Myo1D functions in mature enterocytes (ECs) to control mitotic activity of intestinal stem cells (ISCs). In Myo1D mutant midguts, many signaling events involved in AiP (ROS generation, hemocyte recruitment, and JNK signaling) are affected. Importantly, similar to AiP, Myo1D is required for membrane localization of Dronc in ECs. We propose that ECs destined to die transiently enter an undead-like state through Myo1D-dependent membrane localization of Dronc, which enables them to generate signals for ISC activity and their replacement. The concept of transiently ‘‘undead’’ cells may be relevant for other stem cell models in flies and mammals. Amcheslavsky et al. reveal a mechanism according to which apoptotic cells maintain survival transiently by entering an ‘‘undead’’-like state through membrane localization of Dronc in a Myo1D-dependent manner. This transient ‘‘undead’’-like state enables apoptotic cells for a short time to generate signals for mitotic activity of stem cells.
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