Journal
INTEGRATIVE BIOLOGY
Volume 13, Issue 2, Pages 31-43Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intbio/zyaa027
Keywords
pericyte; endothelial cell; angiogenesis; cell migration; proliferation; time-lapse imaging
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Funding
- National Institutes of Health [R01-HL146596, R01-AG049821]
- National Science Foundation [1752339]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1752339] Funding Source: National Science Foundation
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Pericytes play critical roles in vascular remodeling, with research using tissue explant models showing that pericytes detach, migrate, and proliferate in synchrony with endothelial cells during the process.
Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing 'double reporter' animals with fluorescently-labeled pericytes and endothelial cells (via Ng2:DsRed and Flk-1:eGFP genes, respectively). Time-lapse confocal imaging of active vessel remodeling within adult connective tissues and embryonic skin revealed a subset of pericytes detaching and migrating away from the vessel wall. Vessel-associated pericytes displayed rapid filopodial sampling near sprouting endothelial cells that emerged from parent vessels to form nascent branches. Pericytes near angiogenic sprouts were also more migratory, initiating persistent and directional movement along newly forming vessels. Pericyte cell divisions coincided more frequently with elongating endothelial sprouts, rather than sprout initiation sites, an observation confirmed with in vivo data from the developing mouse brain. Taken together, these data suggest that (i) pericyte detachment from the vessel wall may represent an important physiological process to enhance endothelial cell plasticity during vascular remodeling, and (ii) pericyte migration and proliferation are highly synchronized with endothelial cell behaviors during the coordinated expansion of a vascular network.
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