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

Stem Cells. 2023 Jun 15;41(6):570-577. doi: 10.1093/stmcls/sxad034.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Movement / physiology
  • Chemokine CXCL12* / metabolism
  • Ischemia / metabolism
  • Mice
  • Neural Stem Cells* / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism

Substances

  • Chemokine CXCL12
  • Receptors, CXCR4