Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord

J Exp Med. 2021 Aug 2;218(8):e20210040. doi: 10.1084/jem.20210040. Epub 2021 Jun 16.

Abstract

The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not conducive to regeneration and repair. A better understanding of this dichotomy is critical to developing effective therapeutics that target the appropriate pathobiology, but a major challenge has been the large cellular heterogeneity that results in immensely complex cellular interactions. In this study, we used single-cell RNA sequencing to assess virtually all cell types that comprise the mouse spinal cord injury site. In addition to discovering novel subpopulations, we used expression values of receptor-ligand pairs to identify signaling pathways that are predicted to regulate specific cellular interactions during angiogenesis, gliosis, and fibrosis. Our dataset is a valuable resource that provides novel mechanistic insight into the pathobiology of not only spinal cord injury but also other traumatic disorders of the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietins / metabolism
  • Animals
  • Astrocytes / metabolism
  • Cell Communication*
  • Chemotaxis
  • Female
  • Fibroblasts / metabolism
  • Fibrosis
  • Gliosis / complications
  • Gliosis / pathology
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Ligands
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / pathology
  • Neuroglia / pathology
  • Oncostatin M / metabolism
  • Receptors, Oncostatin M / metabolism
  • Signal Transduction
  • Single-Cell Analysis*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / pathology*
  • Time Factors
  • Transcriptome / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiopoietins
  • Interleukin-6
  • Ligands
  • Receptors, Oncostatin M
  • Vascular Endothelial Growth Factor A
  • Oncostatin M