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果蝇卵巢中的干细胞生态位组织需要细胞外基质成分 Perlecan。

Stem cell niche organization in the Drosophila ovary requires the ECM component Perlecan.

机构信息

Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide/JA, Carretera de Utrera km 1, 41013 Sevilla, Spain.

The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 1QN, UK; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool St, Hobart, TAS 7000, Australia.

出版信息

Curr Biol. 2021 Apr 26;31(8):1744-1753.e5. doi: 10.1016/j.cub.2021.01.071. Epub 2021 Feb 22.

Abstract

Stem cells reside in specialized microenvironments or niches that balance stem cell proliferation and differentiation. The extracellular matrix (ECM) is an essential component of most niches, because it controls niche homeostasis, provides physical support, and conveys extracellular signals. Basement membranes (BMs) are thin ECM sheets that are constituted mainly by Laminins, Perlecan, Collagen IV, and Entactin/Nidogen and surround epithelia and other tissues. Perlecans are secreted proteoglycans that interact with ECM proteins, ligands, receptors, and growth factors such as FGF, PDGF, VEGF, Hedgehog, and Wingless. Thus, Perlecans have structural and signaling functions through the binding, storage, or sequestering of specific ligands. We have used the Drosophila ovary to assess the importance of Perlecan in the functioning of a stem cell niche. Ovarioles in the adult ovary are enveloped by an ECM sheath and possess a tapered structure at their anterior apex termed the germarium. The anterior tip of the germarium hosts the germline niche, where two to four germline stem cells (GSCs) reside together with a few somatic cells: terminal filament cells (TFCs), cap cells (CpCs), and escort cells (ECs). We report that niche architecture in the developing gonad requires trol, that niche cells secrete an isoform-specific Perlecan-rich interstitial matrix, and that DE-cadherin-dependent stem cell-niche adhesion necessitates trol. Hence, we provide evidence to support a structural role for Perlecan in germline niche establishment during larval stages and in the maintenance of a normal pool of stem cells in the adult niche.

摘要

干细胞驻留在专门的微环境或龛位中,以平衡干细胞的增殖和分化。细胞外基质 (ECM) 是大多数龛位的重要组成部分,因为它控制着龛位的动态平衡,提供物理支撑,并传递细胞外信号。基底膜 (BM) 是由层粘连蛋白、Perlecan、胶原 IV 和 Entactin/Nidogen 组成的薄 ECM 片,包围着上皮和其他组织。Perlecan 是一种分泌型蛋白聚糖,与 ECM 蛋白、配体、受体和生长因子(如 FGF、PDGF、VEGF、Hedgehog 和 Wingless)相互作用。因此,Perlecan 通过结合、储存或隔离特定配体具有结构和信号功能。我们使用果蝇卵巢来评估 Perlecan 在干细胞龛位功能中的重要性。成年卵巢中的卵小管被 ECM 鞘包裹,并在其前端顶点具有称为生殖质的锥形结构。生殖质的前端尖端容纳生殖细胞龛位,其中有两到四个生殖干细胞 (GSCs) 与少数体细胞一起存在:端丝细胞 (TFCs)、帽细胞 (CpCs) 和护送细胞 (ECs)。我们报告说,发育中的性腺龛位结构需要 trol,龛位细胞分泌一种同种型特异性的富含 Perlecan 的间质基质,DE-cadherin 依赖性的干细胞-龛位黏附需要 trol。因此,我们提供的证据支持 Perlecan 在幼虫阶段生殖细胞龛位建立和成年龛位中维持正常干细胞池方面的结构作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c608/8405445/fbaf337cf274/gr1.jpg

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