Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan.

IF 17 Q1 CELL BIOLOGY
Nature aging Pub Date : 2025-04-01 Epub Date: 2025-03-31 DOI:10.1038/s43587-025-00840-2
Dongeun Heo, Anya A Kim, Björn Neumann, Valerie N Doze, Yu Kang T Xu, Yevgeniya A Mironova, Jared Slosberg, Loyal A Goff, Robin J M Franklin, Dwight E Bergles
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引用次数: 0

Abstract

Oligodendrocyte progenitor cells (OPCs) are highly dynamic, widely distributed glial cells of the central nervous system responsible for generating myelinating oligodendrocytes throughout life. However, the rates of OPC proliferation and differentiation decline dramatically with aging, which may impair homeostasis, remyelination and adaptive myelination during learning. To determine how aging influences OPCs, we generated a transgenic mouse line (Matn4-mEGFP) and performed single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescence to proliferation and differentiation across the lifespan. We found that aging induces distinct transcriptomic changes in OPCs in different states, including enhanced activation of HIF-1α and WNT pathways. Pharmacological inhibition of these pathways in aged OPCs was sufficient to increase their ability to differentiate in vitro. Ultimately, Matn4-mEGFP mouse line and the sequencing dataset of cortical OPCs across ages will help to define the molecular changes guiding OPC behavior in various physiological and pathological contexts.

小鼠少突胶质前体细胞在整个生命周期中的转录谱。
少突胶质细胞祖细胞(OPCs)是高度动态的,广泛分布于中枢神经系统的胶质细胞,在整个生命过程中负责生成髓鞘少突胶质细胞。然而,随着年龄的增长,OPC的增殖和分化率急剧下降,这可能会损害学习过程中的稳态、再髓鞘形成和适应性髓鞘形成。为了确定衰老如何影响OPCs,我们建立了一个转基因小鼠系(Matn4-mEGFP),并进行了单细胞RNA测序,在整个生命周期中从静止到增殖和分化的关键转变过程中提供了更高的转录变化分辨率。我们发现,衰老在不同状态下诱导OPCs明显的转录组变化,包括HIF-1α和WNT通路的激活增强。在老年OPCs中,这些途径的药理抑制足以增加其体外分化能力。最终,Matn4-mEGFP小鼠系和不同年龄皮质OPC的测序数据集将有助于定义在各种生理和病理背景下指导OPC行为的分子变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.70
自引率
0.00%
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