4.8 Article

Spatial and temporal heterogeneity in the lineage progression of fine oligodendrocyte subtypes

期刊

BMC BIOLOGY
卷 20, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s12915-022-01325-z

关键词

Oligodendrocytes; Lineage progression; Spatial transcriptomics; In situ sequencing; Cortex; Corpus callosum; Spinal cord

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资金

  1. Stockholm University
  2. Knut and Alice Wallenberg Foundation [2019-0107, 2018.0172]
  3. Swedish Research Council [2015-03558, 2019-01360, 2019-01238]
  4. Erling Persson Family Foundation
  5. European Union [681893]
  6. Swedish Brain Foundation [FO2017-0075, FO2018-0162]
  7. Swedish Cancer Society (Cancerfonden) [190394]
  8. Swedish Society for Medical Research (SSMF)
  9. Ming Wai Lau Center for Reparative Medicine
  10. Karolinska Institutet [JUB2019]
  11. Karolinska Institutet
  12. Vinnova [2019-01360] Funding Source: Vinnova
  13. Swedish Research Council [2015-03558, 2019-01360, 2019-01238] Funding Source: Swedish Research Council
  14. Forte [2019-01238] Funding Source: Forte
  15. European Research Council (ERC) [681893] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

In this study, in situ sequencing was used to investigate the spatial heterogeneity of oligodendrocyte lineage progression in the brain and spinal cord. The results showed regional and temporal differences in the abundances and population dynamics of oligodendrocyte populations, as well as differences in the timing of oligodendrocyte differentiation and myelination. These findings are important for further understanding the functional heterogeneity of oligodendroglia, particularly in the context of injury or disease.
Background Oligodendrocytes are glial cells that support and insulate axons in the central nervous system through the production of myelin. Oligodendrocytes arise throughout embryonic and early postnatal development from oligodendrocyte precursor cells (OPCs), and recent work demonstrated that they are a transcriptional heterogeneous cell population, but the regional and functional implications of this heterogeneity are less clear. Here, we apply in situ sequencing (ISS) to simultaneously probe the expression of 124 marker genes of distinct oligodendrocyte populations, providing comprehensive maps of the corpus callosum, cingulate, motor, and somatosensory cortex in the brain, as well as gray matter (GM) and white matter (WM) regions in the spinal cord, at postnatal (P10), juvenile (P20), and young adult (P60) stages. We systematically compare the abundances of these populations and investigate the neighboring preference of distinct oligodendrocyte populations. Results We observed that oligodendrocyte lineage progression is more advanced in the juvenile spinal cord compared to the brain, corroborating with previous studies. We found myelination still ongoing in the adult corpus callosum while it was more advanced in the cortex. Interestingly, we also observed a lateral-to-medial gradient of oligodendrocyte lineage progression in the juvenile cortex, which could be linked to arealization, as well as a deep-to-superficial gradient with mature oligodendrocytes preferentially accumulating in the deeper layers of the cortex. The ISS experiments also exposed differences in abundances and population dynamics over time between GM and WM regions in the brain and spinal cord, indicating regional differences within GM and WM, and we found that neighboring preferences of some oligodendroglia populations are altered from the juvenile to the adult CNS. Conclusions Overall, our ISS experiments reveal spatial heterogeneity of oligodendrocyte lineage progression in the brain and spinal cord and uncover differences in the timing of oligodendrocyte differentiation and myelination, which could be relevant to further investigate functional heterogeneity of oligodendroglia, especially in the context of injury or disease.

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