Lee Joo Yeun, Chen Jessica Y, Shaw Jillian L, Chang Karen T
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States of America.
PLoS Genet. 2016 May 18;12(5):e1006043. doi: 10.1371/journal.pgen.1006043. eCollection 2016 May.
Stem cells depend critically on the surrounding microenvironment, or niche, for their maintenance and self-renewal. While much is known about how the niche regulates stem cell self-renewal and differentiation, mechanisms for how the niche is maintained over time are not well understood. At the apical tip of the Drosophila testes, germline stem cells (GSCs) and somatic stem cells share a common niche formed by hub cells. Here we demonstrate that a novel protein named Shriveled (Shv) is necessary for the maintenance of hub/niche integrity. Depletion of Shv protein results in age-dependent deterioration of the hub structure and loss of GSCs, whereas upregulation of Shv preserves the niche during aging. We find Shv is a secreted protein that modulates DE-cadherin levels through extracellular activation of integrin signaling. Our work identifies Shv as a novel activator of integrin signaling and suggests a new integration model in which crosstalk between integrin and DE-cadherin in niche cells promote their own preservation by maintaining the niche architecture.
干细胞的维持和自我更新严重依赖于周围的微环境,即生态位。虽然关于生态位如何调节干细胞的自我更新和分化已有很多了解,但生态位如何随时间维持的机制仍不清楚。在果蝇睾丸的顶端,生殖系干细胞(GSCs)和体细胞干细胞共享一个由枢纽细胞形成的共同生态位。在这里,我们证明了一种名为萎缩蛋白(Shv)的新蛋白对于维持枢纽/生态位的完整性是必需的。Shv蛋白的缺失导致枢纽结构随年龄增长而退化以及生殖系干细胞的丢失,而Shv的上调则在衰老过程中维持生态位。我们发现Shv是一种分泌蛋白,它通过整合素信号的细胞外激活来调节DE-钙黏蛋白水平。我们的工作将Shv鉴定为整合素信号的一种新型激活剂,并提出了一种新的整合模型,即生态位细胞中整合素和DE-钙黏蛋白之间的相互作用通过维持生态位结构来促进它们自身的保存。