Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity
Open Access
- 26 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (9), eabd8811
- https://doi.org/10.1126/sciadv.abd8811
Abstract
The innate immune response influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific transcriptomics and single-cell RNA sequencing to uncover not only a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial cell states even in healthy spinal cord. Upon injury, IAM progressively acquired overall reparative, yet diversified transcriptional profiles, each comprising four transcriptional subtypes with specialized tasks. Notably, IAM have both distinct and common gene signatures as compared to neurodegeneration-associated microglia, both engaging phagocytosis, autophagy, and TyroBP pathways. We also identified an immediate response microglia subtype serving as a source population for microglial transformation and a proliferative subtype controlled by the epigenetic regulator histone deacetylase 3 (HDAC3). Together, our data unveil diversification of myeloid and glial subtypes in SCI and an extensive influence of HDAC3, which may be exploited to enhance functional recovery.Keywords
Funding Information
- National Institutes of Health (R01/R56 NS073596)
- National Institutes of Health (R01 AG046170, RF1 AG054014, U01 AG052411, RF1 AG057440, R01 AG057907)
- Craig H. Neilsen Foundation (476516)
- Deutsche Forschungsgemeinschaft (FR2938/7-1, FR2938/10-1)
- Chinese Scholarship Council
- New York State Spinal Cord Injury Research Board (DOH01-C30603GG, DOH01-C30832GG)
- New York State Spinal Cord Injury Research Board (DOH01-C32634GG)
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