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硫酸乙酰肝素蛋白聚糖分子、 syndecan 和 perlecan 在维持果蝇生殖干细胞中具有不同的作用。

Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells.

机构信息

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan.

RIKEN Center for Sustainable Resource Science, Yokohama, Japan.

出版信息

Dev Growth Differ. 2021 Aug;63(6):295-305. doi: 10.1111/dgd.12741. Epub 2021 Aug 15.

Abstract

The Drosophila female germline stem cell (GSC) niche provides an excellent model for understanding the stem cell niche in vivo. The GSC niche is composed of stromal cells that provide growth factors for the maintenance of GSCs and the associated extracellular matrix (ECM). Although the function of stromal cells/growth factors has been well studied, the function of the ECM in the GSC niche is largely unknown. In this study, we investigated the function of syndecan and perlecan, molecules of the heparan sulfate proteoglycan (HSPG) family, as the main constituents of the ECM. We found that both of these genes were expressed in niche stromal cells, and knockdown of them in stromal cells decreased GSC number, indicating that these genes are important niche components. Interestingly, our genetic analysis revealed that the effects of syndecan and perlecan on the maintenance of GSC were distinct. While the knockdown of perlecan in the GSC niche increased the number of cystoblasts, a phenotype suggestive of delayed differentiation of GSCs, the same was not true in the context of syndecan. Notably, the overexpression of syndecan and perlecan did not cause an expansion of the GSC niche, opposing the results reported in the context of glypican, another HSPG gene. Altogether, our data suggest that HSPG genes contribute to the maintenance of GSCs through multiple mechanisms, such as the control of signal transduction, and ligand distribution/stabilization. Therefore, our study paves the way for a deeper understanding of the ECM functions in the stem cell niche.

摘要

果蝇雌性生殖干细胞 (GSC) 巢区为理解体内干细胞巢区提供了一个极好的模型。GSC 巢区由基质细胞组成,这些基质细胞为 GSCs 的维持和相关细胞外基质 (ECM) 提供生长因子。尽管基质细胞/生长因子的功能已经得到了很好的研究,但 ECM 在 GSC 巢区中的功能在很大程度上仍然未知。在这项研究中,我们研究了 syndecan 和 perlecan 这两个分子作为 ECM 的主要成分在 GSC 巢区中的功能。我们发现这两个基因都在巢区基质细胞中表达,而基质细胞中它们的敲低会导致 GSC 数量减少,这表明这些基因是巢区的重要组成部分。有趣的是,我们的遗传分析表明,syndecan 和 perlecan 对 GSC 维持的影响是不同的。虽然 perlecan 在 GSC 巢区中的敲低会增加cystoblast 的数量,这是 GSCs 分化延迟的表型,但在 syndecan 的情况下则不是如此。值得注意的是,syndecan 和 perlecan 的过表达并没有导致 GSC 巢区的扩张,这与另一个 HSPG 基因 glypican 的报告结果相反。总的来说,我们的数据表明 HSPG 基因通过多种机制,如信号转导的控制和配体的分布/稳定化,有助于 GSCs 的维持。因此,我们的研究为深入了解 ECM 在干细胞巢区中的功能铺平了道路。

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