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Published on: September 12, 2012
Loss of LRP1 in Adult Neural Stem Cells Impairs Migration to Ischemic Lesions
Kristi Dietert1, Swetha Mahesula1, Sheetal Hegde1
1University of Texas Health San Antonio, TX, USA.
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.
Insights
Low-density lipoprotein receptor related protein 1 (LRP1) regulates CXCR4 expression in neural stem cells, impacting their migration to brain injury sites after ischemia. This discovery reveals a new mechanism for neural stem cell response.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Molecular Biology
Background:
- Ischemia triggers stromal-derived factor 1 (SDF1) release in the brain.
- SDF1 activates chemokine receptor CXCR4, guiding neural stem cell migration to injury sites.
Purpose of the Study:
- To identify novel regulators of CXCR4 in neural stem cells.
- To investigate the role of low-density lipoprotein receptor related protein 1 (LRP1) in neural stem cell migration.
Main Methods:
- Generated Nestin-driven LRP1 knockout mice with td-tomato labeled neural stem cells.
- Assessed neural stem cell localization to ischemic lesions.
- Evaluated CXCR4-mediated migration in vitro.
Main Results:
- Reduced migration of td-tomato positive neural stem cells to the lesion in LRP1 knockout mice.
- Disrupted CXCR4-mediated neural stem cell migration in vitro.
- LRP1 appears to mediate CXCR4 expression in vivo, affecting stem cell homing.
Conclusions:
- Low-density lipoprotein receptor related protein 1 (LRP1) is a novel regulator of CXCR4 in neural stem cells.
- The LRP1-CXCR4 interaction influences neural stem cell migration to ischemic brain injury.
- This finding has implications for understanding neural stem cell physiology and therapeutic strategies.
