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

Kristi Dietert; Swetha Mahesula; Sheetal Hegde; John Verschelde; Pamela Reed; Shane Sprague; Erzsebet Kokovay; Naomi L. Sayre

doi:10.1093/stmcls/sxad034

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

Kristi Dietert, Swetha Mahesula, Sheetal Hegde, John Verschelde, Pamela Reed, Shane Sprague, Erzsebet Kokovay, Naomi L. Sayre

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Pages (from-to)	570-577
Number of pages	8
Journal	Stem Cells
Volume	41
Issue number	6
DOIs	https://doi.org/10.1093/stmcls/sxad034
State	Published - Jun 2023

ASJC Scopus subject areas

General Medicine

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title = "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.",

author = "Kristi Dietert and Swetha Mahesula and Sheetal Hegde and John Verschelde and Pamela Reed and Shane Sprague and Erzsebet Kokovay and Sayre, {Naomi L.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press.",

year = "2023",

month = jun,

doi = "10.1093/stmcls/sxad034",

language = "English (US)",

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TY - JOUR

T1 - Loss of LRP1 in Adult Neural Stem Cells Impairs Migration to Ischemic Lesions

AU - Dietert, Kristi

AU - Mahesula, Swetha

AU - Hegde, Sheetal

AU - Verschelde, John

AU - Reed, Pamela

AU - Sprague, Shane

AU - Kokovay, Erzsebet

AU - Sayre, Naomi L.

N1 - Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

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

Abstract

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