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

• Published in: Cell reports (Cambridge) Vol. 42; no. 5; p. 112486
• Main Authors: Wei, Haichao, Wu, Xizi, Withrow, Joseph, Cuevas-Diaz Duran, Raquel, Singh, Simranjit, Chaboub, Lesley S., Rakshit, Jyotirmoy, Mejia, Julio, Rolfe, Andrew, Herrera, Juan J., Horner, Philip J., Wu, Jia Qian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2023; Elsevier
• Subjects: astrocyte lineage; Astrocytes; CP: Neuroscience; CP: Stem cell research; GFAP-expressing cells; glial progenitor heterogeneity; Humans; key regulators; Neuroglia; Neurons; Sequence Analysis, RNA; Spinal Cord; Spinal Cord Injuries - genetics; spinal cord injury; glial progenitor heterogeneity; spinal cord injury; key regulators; CP: Stem cell research; CP: Neuroscience; astrocyte lineage; GFAP-expressing cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112486

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. [Display omitted] •scRNA-seq revealed GFAP+ populations with distinct functional enrichment and dynamics•Regulatory network analysis predicted regulons defining specific subpopulations•Laminectomy sham surgery was sufficient to induce the activation of astrocyte-lineage cells•This study unveiled additional sources/pools of resident progenitors in adult spinal cord Wei et al. report the identification of the subpopulations of GFAP-expressing cells in healthy and injured adult spinal cords using single-cell RNA-seq. Bioinformatic and functional investigations of these subpopulations revealed the signature, location, morphology, and proliferation and differentiation abilities of the resident progenitors in the spinal cord.