Diversified Transcriptional Responses of Myeloid and Glial Cells in Spinal Cord Injury Shaped by HDAC3 Activity

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Feb 27

PMID 33637528

Citations 27

Authors

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

Affiliations

Soon will be listed here.

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.

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