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Atp13a5 Marker Reveals Pericyte Specification in the Mouse Central Nervous System
Xinying Guo1,2, Shangzhou Xia3, Tenghuan Ge3
1Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, California 90033 sarah_guoxy@163.com qma@llu.edu zzhao@usc.edu.
Researchers identified a new marker, cation-transporting ATPase 13A5 (Atp13a5), specific to central nervous system (CNS) pericytes. An Atp13a5-based mouse model reliably labels these cells, aiding research into pericyte function and blood-brain barrier integrity.
Area of Science:
- Neuroscience
- Vascular Biology
- Genetics
Background:
- Perivascular mural cells, including vascular smooth muscle cells and pericytes, are crucial for vascular health.
- In the central nervous system (CNS), pericytes are vital for blood-brain barrier (BBB), blood-spinal cord barrier, and blood-retinal barrier functions.
- Genetic and molecular distinctions between CNS and peripheral pericytes remain unclear, hindering the development of specific research models.
Purpose of the Study:
- To identify a novel, specific marker for central nervous system (CNS) pericytes.
- To develop a reliable genetic tool for studying CNS pericytes and their role in health and disease.
- To investigate the developmental timing and distribution of CNS pericytes.
Main Methods:
- Single-cell transcriptomics to identify potential CNS pericyte markers.
- Generation of a knock-in mouse model expressing tdTomato reporter and Cre recombinase under the control of the identified marker.
- Utilizing the reporter model for tracing pericyte distribution in vivo.
Main Results:
- Cation-transporting ATPase 13A5 (Atp13a5) was identified as a specific marker for brain pericytes via single-cell transcriptomics.
- The Atp13a5-based reporter model accurately labels CNS pericytes in the brain, spinal cord, and retina, but not in peripheral organs.
- Atp13a5-positive pericytes emerge around embryonic day 15 (E15) and distribute along the cerebrovasculature, suggesting developmental regulation by the neural environment.
Conclusions:
- Atp13a5 serves as a specific marker for the central nervous system (CNS) pericyte lineage.
- The developed Atp13a5-based mouse model is a valuable tool for investigating CNS pericyte heterogeneity and blood-brain barrier functions.
- This research facilitates further exploration of pericyte roles in neurological health and disease.
