Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity

Shalaka Wahane, Xianxiao Zhou, Xiang Zhou, Lei Guo, Marie Sophie Friedl, Michael Kluge, Aarthi Ramakrishnan, Li Shen, Caroline C. Friedel, Bin Zhang, Roland H. Friedel, Hongyan Zou

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Article numbereabd8811
JournalScience advances
Volume7
Issue number9
DOIs
StatePublished - 24 Feb 2021

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