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基质细胞景观控制体内生殖细胞命运。

The matrisome landscape controlling in vivo germ cell fates.

机构信息

Department of Experimental Medical Science, Lund University, Lund, Sweden.

Lund Stem Cell Center, Lund University, Lund, Sweden.

出版信息

Nat Commun. 2024 May 17;15(1):4200. doi: 10.1038/s41467-024-48283-4.

Abstract

The developmental fate of cells is regulated by intrinsic factors and the extracellular environment. The extracellular matrix (matrisome) delivers chemical and mechanical cues that can modify cellular development. However, comprehensive understanding of how matrisome factors control cells in vivo is lacking. Here we show that specific matrisome factors act individually and collectively to control germ cell development. Surveying development of undifferentiated germline stem cells through to mature oocytes in the Caenorhabditis elegans germ line enabled holistic functional analysis of 443 conserved matrisome-coding genes. Using high-content imaging, 3D reconstruction, and cell behavior analysis, we identify 321 matrisome genes that impact germ cell development, the majority of which (>80%) are undescribed. Our analysis identifies key matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior. Further, our results demonstrate that germ cell development requires continual remodeling of the matrisome landscape. Together, this study provides a comprehensive platform for deciphering how extracellular signaling controls cellular development and anticipate this will establish new opportunities for manipulating cell fates.

摘要

细胞的发育命运受内在因素和细胞外环境的调控。细胞外基质(基质组)传递化学和机械线索,这些线索可以改变细胞的发育。然而,我们对基质因子如何在体内控制细胞的全面理解还很缺乏。在这里,我们表明特定的基质因子单独和集体地控制生殖细胞的发育。通过对秀丽隐杆线虫生殖系中未分化的生殖干细胞到成熟卵子的发育进行调查,我们对 443 个保守的基质编码基因进行了全面的功能分析。使用高内涵成像、3D 重建和细胞行为分析,我们确定了 321 个影响生殖细胞发育的基质基因,其中大多数(>80%)是以前未描述的。我们的分析确定了自主和非自主作用的关键基质网络,以协调生殖细胞的行为。此外,我们的结果表明,生殖细胞的发育需要不断重塑基质组景观。总之,这项研究提供了一个全面的平台,用于破译细胞外信号如何控制细胞的发育,并预计这将为操纵细胞命运开辟新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b329/11101451/cf45bb07520a/41467_2024_48283_Fig1_HTML.jpg

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