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

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

Cell Reports, 2023 · DOI: 10.1016/j.celrep.2023.112486 · Published: May 30, 2023

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This study uses single-cell RNA sequencing to analyze GFAP-expressing cells in spinal cord injury models. It identifies and compares subpopulations in acute-stage data. The research verifies the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury. This study expands the knowledge of the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.

Study Duration
1 Month
Participants
GFAP-expressing cells from adult GFAP-Cre:R26-tdT spinal cord
Evidence Level
Not specified

Key Findings

  • 1
    The study identifies distinct subpopulations of GFAP-expressing cells with unique functional enrichment and identities defined by subpopulation-specific transcription factors and regulons.
  • 2
    Intermediate cell populations in adult spinal cord expressing both astrocyte and oligodendrocyte precursor cell markers are uncovered, some subtypes being enriched in neuronal, proliferative, inflammation, oligodendrocyte, or myeloid cell markers.
  • 3
    Resident astrocyte-ependymal cells are found outside the central canal in naive animals, preferentially in white matter, and their numbers increase following sham surgery and further after acute injury. An astrocyte-ependymal-Nestin (Nes)high population is uncovered.

Research Summary

The study employs single-cell RNA sequencing to analyze GFAP-expressing cells in sub-chronic spinal cord injury models, identifying and comparing subpopulations with acute-stage data. The research verifies the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury. The study demonstrates the molecular divergence and dynamics of glial progenitor subpopulations in healthy and injured adult spinal cords, characterizing their differentiation capability and analyzing transcription factors defining cell identity.

Practical Implications

Therapeutic Development

Targeting specific astroglial subpopulations/states could lead to improved therapeutics for spinal cord injury.

Understanding Cell Fate

Dissecting neurogenesis potential and cell fate transitions after injury requires further experimentation.

Enhancing Regeneration

Enhancing the number or promoting de-differentiation toward NSC/NPC-like cells in a chronic injury setting could enhance cell regeneration and plasticity.

Study Limitations

  • 1
    GFAP promoter is not only active in astrocytes but also in progenitors.
  • 2
    Physiological functions of cell types after SCI are not yet dissected.
  • 3
    Whether heterogeneity of astrocyte-lineage cells reflects different cell species or different functional states needs further investigation.

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