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Loss of LRP1 in Adult Neural Stem Cells Impairs Migration to Ischemic Lesions.

ABSTRACT: After ischemia, cells in the brain parenchyma upregulate stromal derived factor 1 (SDF1), driving chemokine receptor CXCR4-mediated migration of adult neural stem cells to the ischemic injury. We discovered a novel regulator of CXCR4 in neural stem cells, low-density lipoprotein receptor related protein 1 (LRP1). We used Nestin-driven knockout of LRP1 and induction of td-tomato in neural stem cells of adult mice. We observed reduced localization of td-tomato positive cells to the lesion, and find disrupted CXCR4-mediated neural stem cell migration in vitro, which is likely driven by LRP1-mediated loss of CXCR4 expression in vivo. Our results suggest that LRP1 is a novel regulator of CXCR4 in neural stem cells. This heretofore unknown interaction between LRP1 and CXCR4 could have significant consequences for multiple aspects of neural stem cell physiology.

SUBMITTER: Dietert K

PROVIDER: S-EPMC10267954 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Loss of LRP1 in Adult Neural Stem Cells Impairs Migration to Ischemic Lesions.

Dietert Kristi K Mahesula Swetha S Hegde Sheetal S Verschelde John J Reed Pamela P Sprague Shane S Kokovay Erzsebet E Sayre Naomi L NL

Stem cells (Dayton, Ohio) 20230601 6

After ischemia, cells in the brain parenchyma upregulate stromal derived factor 1 (SDF1), driving chemokine receptor CXCR4-mediated migration of adult neural stem cells to the ischemic injury. We discovered a novel regulator of CXCR4 in neural stem cells, low-density lipoprotein receptor related protein 1 (LRP1). We used Nestin-driven knockout of LRP1 and induction of td-tomato in neural stem cells of adult mice. We observed reduced localization of td-tomato positive cells to the lesion, and fin ...[more]

PMID: 37186298

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