Glial Progenitor Heterogeneity and Key Regulators Revealed by Single-cell Rna Sequencing Provide Insight to Regeneration in Spinal Cord Injury

Authors

Haichao Wei
Xizi Wu
Joseph Withrow
Raquel Cuevas-Diaz Duran
Simranjit Singh
Lesley S Chaboub
Jyotirmoy Rakshit
Julio Mejia
Andrew Rolfe
Juan J Herrera
Philip J Horner
Jia Qian Wu

Publication Date

5-30-2023

Journal

Cell Reports

Abstract

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury and uncover the populations of the intermediate cells enriched in neuronal genes that could potentially transition into other subpopulations. This study has expanded the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.

Keywords

Humans, Neuroglia, Spinal Cord Injuries, Astrocytes, Neurons, Spinal Cord, Sequence Analysis, RNA