Glial progenitor heterogeneity and key regulators revealed by single-cell RNA sequencing provide insight to regeneration in spinal cord injury

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number112486
JournalCell Reports
Volume42
Issue number5
DOIs
StatePublished - May 30 2023

Keywords

  • CP: Neuroscience
  • CP: Stem cell research
  • GFAP-expressing cells
  • astrocyte lineage
  • glial progenitor heterogeneity
  • key regulators
  • spinal cord injury
  • Astrocytes
  • Neurons
  • Humans
  • Neuroglia
  • Spinal Cord Injuries/genetics
  • Sequence Analysis, RNA
  • Spinal Cord

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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