Repopulation of microglia and its implications for CNS disorders: Insights from the single-cell era

Cong Chen1, Guanjia Qiao2, Dantong Tang1

  • 1Department of Neurology, First Hospital of China Medical University, Shenyang, Liaoning Province, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, China; Shenyang Clinical Medical Research Center for Difficult and Serious Diseases of the Nervous System, China.

Neurobiology of Disease
|August 27, 2025
PubMed

Insights

Microglia repopulation strategies, targeting colony-stimulating factor receptor 1 (CSF1R) inhibitors, show therapeutic potential for central nervous system (CNS) disorders. Single-cell sequencing reveals microglial heterogeneity and self-renewal capacity for novel treatments.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the resident immune cells of the central nervous system (CNS), are crucial for brain health and disease.
  • Understanding microglial origin, development, and heterogeneity is key to developing effective CNS therapies.
  • Colony-stimulating factor receptor 1 (CSF1R) inhibitors offer a method for microglial depletion and subsequent repopulation.

Purpose of the Study:

  • To comprehensively review the origin, development, repopulation dynamics, and heterogeneity of microglia.
  • To highlight the therapeutic potential of microglial repopulation in central nervous system (CNS) disorders.
  • To integrate findings from single-cell sequencing technologies to understand microglial function in health and disease.

Main Methods:

  • Literature review focusing on microglial biology and therapeutic strategies.
  • Analysis of studies utilizing colony-stimulating factor receptor 1 (CSF1R) inhibitors for microglial manipulation.
  • Integration of single-cell RNA sequencing (scRNA-seq) data to characterize microglial subpopulations.

Main Results:

  • CSF1R inhibitors enable effective microglial depletion, with repopulated microglia exhibiting comparable function to controls.
  • Single-cell sequencing reveals diverse microglial subpopulations, including disease-associated microglia (DAM) and neurodegenerative microglia (MGnD).
  • Repopulated microglia possess significant self-renewal, proliferative, and migratory capacities, suggesting therapeutic value.

Conclusions:

  • Microglial repopulation holds significant promise for treating central nervous system (CNS) disorders.
  • Understanding microglial heterogeneity via single-cell technologies is vital for advancing therapeutic strategies.
  • Further research into microglial repopulation mechanisms can unlock novel treatment avenues for neurological diseases.