Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury

Cell Death and Disease, 2022 · DOI: 10.1038/s41419-022-04864-z · Published: May 12, 2022

Simple Explanation

Spinal cord injury (SCI) causes inflammation, which can either help or hinder recovery. Microglia, immune cells in the central nervous system, play a crucial role in this process. This study investigates how microglia repopulate after SCI and what factors regulate this process. Using single-cell RNA sequencing, the researchers mapped the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. They discovered that microglia initially decrease but then repopulate, while other immune cells infiltrate the injured area. The study found that the repopulation of microglia is derived from residual microglia after SCI. Furthermore, they identified Hif1α as a key factor promoting microglial proliferation and functional recovery after SCI.

Study Duration

Not specified

Participants

Mice (C57/BL6 background)

Evidence Level

Not specified

Key Findings

1
Microglia repopulation after SCI is primarily derived from residual microglia, not from nestin+ stem cells.
2
Residual microglia regress to a developmental growth state in the early stages after SCI, facilitating their proliferation.
3
Hif1α promotes microglial proliferation and is essential for axon regeneration and functional recovery after SCI. Ablation of Hif1α in microglia results in larger lesion sizes and impaired functional recovery.

Research Summary

This study used single-cell RNA sequencing to analyze immune cell dynamics after spinal cord injury (SCI) in mice, revealing the heterogeneity of immune cells and the repopulation of microglia. The research found that microglia repopulation is derived from residual microglia that regress to a developmental growth state, and that Hif1α promotes microglial proliferation and functional recovery after SCI. Targeting Hif1α may help in axon regeneration and functional recovery after SCI, suggesting a potential therapeutic strategy.

Practical Implications

Therapeutic Target Identification

Hif1α is identified as a potential therapeutic target to promote microglial repopulation, axon regeneration, and functional recovery after SCI.

Understanding Immune Response

The study provides a comprehensive understanding of the dynamic changes in immune cell populations after SCI, which can inform the development of targeted immunotherapies.

Microglia Origin Confirmation

The research confirms that resident microglia, rather than stem cells, primarily contribute to microglia repopulation after SCI, focusing future research on mechanisms driving resident microglial proliferation.

Study Limitations

1
The study is conducted in mice, and the results may not be directly translatable to humans.
2
The functions of Hif1α activation in other cell types (astrocytes, neurons, oligodendrocytes, and ﬁbroblasts) need to be examined.
3
The detailed mechanisms by which immature neutrophils contribute to regeneration need to be further explored.

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