小鼠脊髓损伤时空分子图谱确定了一个独特的星形胶质细胞亚群和 IGFBP2 的治疗潜力

IF 10.7 1区 生物学 Q1 CELL BIOLOGY
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引用次数: 0

摘要

脊髓损伤(SCI)会引发一连串错综复杂的分子和细胞变化,从而决定脊髓损伤的结果。在这项研究中,我们解析了损伤小鼠脊髓的时空组织,并对脊髓损伤后的原位细胞-细胞通讯进行了定量评估。通过分析现有的单细胞 RNA 测序数据集和我们的空间数据,我们划分出了一个表达 Igfbp2 的星形胶质细胞亚群,它们从白质(WM)迁移到灰质(GM),并在 SCI 后发生反应,被称为 Astro-GMii。此外,Igfbp2 的上调促进了星形胶质细胞的迁移、增殖和反应性,分泌的 IGFBP2 蛋白促进了神经元的生长。最后,我们发现 IGFBP2 能显著减少 SCI 小鼠模型中神经元的损失,并明显改善其体内功能的恢复。总之,这项研究不仅提供了一个全面的 SCI 分子图谱,而且例证了如何应用这一丰富的资源赋予细胞和基因以功能洞察力和治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2

A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2

Spinal cord injury (SCI) triggers a cascade of intricate molecular and cellular changes that determine the outcome. In this study, we resolve the spatiotemporal organization of the injured mouse spinal cord and quantitatively assess in situ cell-cell communication following SCI. By analyzing existing single-cell RNA sequencing datasets alongside our spatial data, we delineate a subpopulation of Igfbp2-expressing astrocytes that migrate from the white matter (WM) to gray matter (GM) and become reactive upon SCI, termed Astro-GMii. Further, Igfbp2 upregulation promotes astrocyte migration, proliferation, and reactivity, and the secreted IGFBP2 protein fosters neurite outgrowth. Finally, we show that IGFBP2 significantly reduces neuronal loss and remarkably improves the functional recovery in a mouse model of SCI in vivo. Together, this study not only provides a comprehensive molecular atlas of SCI but also exemplifies how this rich resource can be applied to endow cells and genes with functional insight and therapeutic potential.

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来源期刊
Developmental cell
Developmental cell 生物-发育生物学
CiteScore
18.90
自引率
1.70%
发文量
203
审稿时长
3-6 weeks
期刊介绍: Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.
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