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

Author:

Dietert Kristi1ORCID,Mahesula Swetha1,Hegde Sheetal1,Verschelde John1,Reed Pamela1,Sprague Shane1,Kokovay Erzsebet1,Sayre Naomi L12

Affiliation:

1. University of Texas Health San Antonio , TX , USA

2. South Texas Veteran’s Health Care System San Antonio , TX , USA

Abstract

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.

Funder

National Institutes of Health

National Center for Advancing Translational Sciences

NCI

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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