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A2879 - Pericyte Fate Mapping in Mice with Hypoxia-Induced PAH
Author Block: K. Yuan1, E. Shamskhou2, M. Orcholski3, K. Red-Horse4, V. De Jesus Perez5; 1Medicine, Stanford University, Palo Alto, CA, United States, 2Pulmonary and Critical Care, Stanford University, Palo Alto, CA, United States, 3Dept of Medicine, Stanford Univ, Stanford, CA, United States, 4Biology, Stanford University, Palo Alto, CA, United States, 5Stanford Med Ctr, Palo Alto, CA, United States.
Pericytes are specialized perivascular cells with mesenchymal stem cell-like properties that can give rise to different cell lineages. Little is known regarding the contribution of pericytes to pulmonary vascular disorder, such as pulmonary arterial hypertension (PAH), with major pathological features of muscularized distal arterioles due to excessive proliferation of PASMCs. Whether pericytes can differentiate into PASMCs and contribute to muscularization of distal vessels in PAH remain poorly understood. We utilized fate mapping and develop an approach for generating a timeline of key cellular events during hypoxia-induced PAH using the NG2-TdTomato murine line. After mice were exposed to hypoxia at various time points, lungs were extracted, sliced and stained by different cell markers. Individual red fluorescent cells after hypoxia day 21 were sorted and tested with 48 specific cell markers using the single cell Q-PCR. Under normoxia, red cells were found in the lung parenchyma associated with alveolar capillaries. In hypoxia day 7, red cells were accumulated at distal and continued to approach larger vessels at hypoxia day 14. In hypoxia day 21, red cells attached to the vessels and coexpressing mature SMC markers. Single cell qPCR from cells at hypoxia day 21 demonstrated that 65% expressed SMC markers while the remainder expressed a mixture of pericyte, EC and fibroblast markers. Our results suggest that pericytes contribute to muscularization of distal precapillary vessels in response to hypoxia by differentiating into SMCs. Our findings provide insight into the pathobiology of hypoxia-induced PAH.