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Nature Aging, 31 March 2025 | https://doi.org/10.1038/s43587-025-00840-2
Transcriptional profiles of mouse oligodendrocyte precursor cells across the lifespan
Dongeun Heo 1,5, Anya A. Kim 1, Björn Neumann 2,6, Valerie N. Doze 1, Yu Kang T. Xu 1, Yevgeniya A. Mironova 1, Jared Slosberg 3,4, Loyal A. Goff 1,3,4, Robin J. M. Franklin 2,6 & Dwight E. Bergles 1,4,*
1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA.
2Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
3Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
4Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
5Present address: Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
6Present address: Altos Labs - Cambridge Institute of Science, Granta Park, Cambridge, UK.
2Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
3Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
4Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
5Present address: Vollum Institute, Oregon Health and Science University, Portland, OR, USA.
6Present address: Altos Labs - Cambridge Institute of Science, Granta Park, Cambridge, UK.
*Corresponding author: correspondence to Dwight E. Bergles
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.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-04-04)
- 국외 연구진
- 생명과학 > 신경생물학
관련 웨비나
![노화에 따른 희소돌기아교 전구세포 (oligodendrocyte precursor cell) 전사체 변화 [Nature Aging]](/upload/board/files/onseminar/thumb/thumb_0000934.png)
학술웨비나
노화에 따른 희소돌기아교 전구세포 (oligodendrocyte precursor cell) 전사체 변화 [Nature Aging] 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 novel 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.- 허동은(Oregon Health & Science University)
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