Suppr超能文献

成体果蝇肠道干细胞的定向分化和终末分化需要不同水平的 Notch 活性。

Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine.

机构信息

Institut Pasteur, Developmental Biology Department, F-75015 Paris, France.

出版信息

Development. 2011 Nov;138(21):4585-95. doi: 10.1242/dev.065292. Epub 2011 Sep 28.

Abstract

Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e. exit from self-renewal, and terminal differentiation are controlled by Notch signaling. Here, we show that distinct requirements for Notch activity exist: commitment requires high Notch activity, whereas terminal differentiation can occur with lower Notch activity. We identified the gene GDP-mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being required for commitment but dispensable for terminal differentiation. Gmd loss resulted in aberrant, self-renewing stem cell divisions that generated extra ISC-like cells defective in Notch reporter activation, as well as wild-type-like cell divisions that produced properly terminally differentiated cells. Lowering Notch signaling using additional genetic means, we provided further evidence that commitment has a higher Notch signaling requirement than terminal differentiation. Our work suggests that a commitment requirement for high-level Notch activity safeguards the stem cells from loss through differentiation, revealing a novel role for the importance of Notch signaling levels in this system.

摘要

成体干细胞的自我更新和分化受到严格调控,以确保组织正常维持。在果蝇的肠道中,细胞的定型(即退出自我更新)和终末分化均受到 Notch 信号的调控。在这里,我们发现 Notch 活性存在不同的需求:定型需要高 Notch 活性,而终末分化可以在较低的 Notch 活性下进行。我们发现 GDP-甘露糖 4,6-脱水酶(Gmd)是 Notch 信号的调节剂,它是定型所必需的,但对终末分化是可有可无的。Gmd 的缺失导致了异常的、自我更新的干细胞分裂,产生了缺乏 Notch 报告基因激活的多余 ISC 样细胞,以及产生正常终末分化细胞的野生型样细胞分裂。通过其他遗传手段降低 Notch 信号,我们提供了进一步的证据表明定型比终末分化需要更高水平的 Notch 信号。我们的工作表明,定型需要高水平的 Notch 活性,这可以防止干细胞通过分化而丢失,揭示了 Notch 信号水平在这个系统中的一个新作用。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验