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<p>Functional revascularization is key to stroke recovery and requires remodeling and regeneration of blood vessels around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPCs) are critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and perivascular fibroblasts that together help cerebral microvasculature regenerate following experimental stroke. Ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of <i>Hic1</i><sup><i>+</i></sup> SPCs uncovered a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts. Both populations of these cells remained segregated, displaying distinct angiogenic and fibrogenic profiles. Therefore, pericytes and perivascular fibroblasts are distinct subpopulations of SPCs in the adult brain that coordinate revascularization and scar formation after injury.</p>

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Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke

  • 期刊论文

  • 发表日期：

    2025年2月17日

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  • Louis-Philippe Bernier,
  • Jasmin K. Hefendehl,
  • R. Wilder Scott,
  • Lin Wei Tung,
  • Coral-Ann Lewis,
  • Hesham Soliman,
  • Stefan Simm,
  • Lasse Dissing-Olesen,
  • Jan Hofmann,
  • David Guo,
  • Murphy DeMeglio,
  • Fabio M. Rossi,
  • T. Michael Underhill,
  • Brian A. MacVicar

摘要

Functional revascularization is key to stroke recovery and requires remodeling and regeneration of blood vessels around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPCs) are critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and perivascular fibroblasts that together help cerebral microvasculature regenerate following experimental stroke. Ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of Hic1+ SPCs uncovered a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts. Both populations of these cells remained segregated, displaying distinct angiogenic and fibrogenic profiles. Therefore, pericytes and perivascular fibroblasts are distinct subpopulations of SPCs in the adult brain that coordinate revascularization and scar formation after injury.