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SMAlow/undetectable pericytes differentiate into microglia- and macrophage-like cells in ischemic brain

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Abstract

Pericytes are multipotent perivascular cells that play important roles in CNS injury. However, controversial findings exist on how pericytes change and whether they differentiated into microglia-like cells after ischemic stroke. This discrepancy is mainly due to the lack of pericyte-specific markers: the “pericyte” population identified in previous studies contained vascular smooth muscle cells (vSMCs) and/or fibroblasts. Therefore, it remains unclear which cell type differentiates into microglia-like cells after stroke. In this study, lineage-tracing technique was used to mark α-smooth muscle actin (SMA)low/undetectable pericytes, vSMCs, and fibroblasts, and their fates were analyzed after ischemic stroke. We found that SMAlow/undetectable pericytes and fibroblasts but not vSMCs substantially proliferated at the subacute phase after injury, and that SMAlow/undetectable pericyte but not vSMCs or fibroblasts differentiated into Iba1+ cells after ischemic stroke. Further imaging flow cytometry analysis revealed that SMAlow/undetectable pericytes differentiated into both microglia and macrophages at day 7 after stroke. These results demonstrate that SMAlow/undetectable pericytes rather than vSMCs or fibroblasts differentiate into both microglia-like and macrophage-like cells after stroke, suggesting that these pericytes may be targeted in the treatment of ischemic stroke.

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Data availability

All data generated in this study are available in this article and the online supplementary material.

Abbreviations

Cas3:

Caspase 3

CCA:

Common carotid artery

Col1α1:

Alpha-1 type I collagen

DPI:

Days post-injury

ECA:

External carotid artery

ECM:

Extracellular matrix

ICA:

Internal carotid artery

MCAO:

Middle cerebral artery occlusion

SMA:

α-Smooth muscle actin

vSMCs:

Vascular smooth muscle cell

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Acknowledgements

We would like to thank Dr. Volkhard Lindner for the PDGFRβ-Cre mice.

Funding

This work was partially supported by NIH Grants (R01HL146574, RF1AG065345, R21AG064422, and R21AG073862) and AHA Grant (16SDG29320001) to YY.

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  1. Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC8, Tampa, FL, 33612, USA

    Abhijit Nirwane & Yao Yao

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Conceptualization, YY; Methodology, AN and YY; Analysis, AN; Writing, AN and YY; Funding Acquisition, YY; Supervision, YY.

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Correspondence to Yao Yao.

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Nirwane, A., Yao, Y. SMAlow/undetectable pericytes differentiate into microglia- and macrophage-like cells in ischemic brain. Cell. Mol. Life Sci. 79, 264 (2022). https://doi.org/10.1007/s00018-022-04322-1

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