Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila.
Escargot controls somatic stem cell maintenance through the attenuation of the insulin receptor pathway in Drosophila.
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DOI：
10.1016/j.celrep.2022.110679
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发表时间：
2022-04-19
期刊：
影响因子：
8.8
通讯作者：
Jones, D. Leanne
中科院分区：
文献类型：
--
作者：
Demarco, Rafael Senos;Stack, Brian J.;Tang, Alexander M.;Voog, Justin;Sandall, Sharsti L.;Southall, Tony D.;Brand, Andrea H.;Jones, D. Leanne
成体干细胞协调内在和外在，局部和全身的线索，以保持自我更新和分化之间的适当平衡。然而，干细胞用于整合这些信号的精确机制仍然难以捉摸。在这里，我们表明，蜗牛（Esg），转录因子的蜗牛家族的成员，调节维持体细胞囊肿干细胞（CySC）在果蝇睾丸通过减弱促分化胰岛素受体（InR）途径的活性。Esg正调控胰岛素信号传导拮抗剂ImpL2的表达，同时也减弱InR的表达。此外，需要Esg介导的InR途径的抑制来抑制响应于饥饿的CySC损失。考虑到蜗牛家族转录因子的保守性，表征Esg在体内平衡和营养可用性下降期间调节细胞命运决定的机制可能会提供对其他组织和生物体中干细胞行为的代谢调节的深入了解。体细胞囊肿干细胞（CySC）的维持需要蜗牛（Esg）Esg减弱囊肿干细胞（CySC）中的胰岛素受体（InR）途径Esg刺激胰岛素拮抗剂ImpL 2的表达并抑制InR Esg介导的InR抑制是饥饿条件下干细胞保存所需的。显示转录因子Escargot控制果蝇睾丸中的体干细胞命运。从机制上讲，蜗牛抑制干细胞中的胰岛素受体（InR）信号传导，以防止分化。在体内平衡和饥饿期间，干细胞的保存需要通过蜗牛抑制INR信号传导。
Adult stem cells coordinate intrinsic and extrinsic, local and systemic, cues to maintain the proper balance between self-renewal and differentiation. However, the precise mechanisms stem cells use to integrate these signals remain elusive. Here, we show that Escargot (Esg), a member of the Snail family of transcription factors, regulates the maintenance of somatic cyst stem cells (CySCs) in the Drosophila testis by attenuating the activity of the pro-differentiation insulin receptor (InR) pathway. Esg positively regulates the expression of an antagonist of insulin signaling, ImpL2, while also attenuating the expression of InR. Furthermore, Esg-mediated repression of the InR pathway is required to suppress CySC loss in response to starvation. Given the conservation of Snail-family transcription factors, characterizing the mechanisms by which Esg regulates cell-fate decisions during homeostasis and a decline in nutrient availability is likely to provide insight into the metabolic regulation of stem cell behavior in other tissues and organisms. Escargot (Esg) is required for somatic cyst stem cell (CySC) maintenance Esg attenuates the insulin receptor (InR) pathway in cyst stem cells (CySCs) Esg stimulates expression of the insulin antagonist ImpL2 and represses InR Esg-mediated InR suppression is needed for stem cell preservation under starvation Sênos Demarco et al. show that the transcription factor Escargot controls somatic stem cell fate in the Drosophila testis. Mechanistically, Escargot suppresses insulin receptor (InR) signaling in stem cells to prevent differentiation. InR signaling suppression by Escargot is required for the preservation of stem cells during homeostasis and starvation.
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影响因子：
4.8
作者：
Demarco, Rafael S.;Eikenes, Asmund H.;Haglund, Kaisa;Jones, D. Leanne
通讯作者：
Jones, D. Leanne
影响因子：
9.2
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通讯作者：
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影响因子：
8.8
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64.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Jones, D. Leanne