Pericytes contribute to pulmonary vascular remodeling via HIF2a signaling

Using a combination of single-cell RNAseq methods and murine pulmonary hypertension models, we show HIF2a overexpressing pericytes' transformation into SMC-like cells, confirming HIF2a as a major molecular regulator in hypoxia-induced pulmonary hypertension (PH) and vascular remodeling. We demonstrate that HIF2a overexpression in pericyte-dominant transgenic mice exacerbates PH and right ventricular hypertrophy (RVH), whereas disruption of HIF2a expression attenuates the development of PH. Overall design: NG2-CreERTM (Jax strain 008538) bred with Ai14 tdTomato lines in order to get NG2 cell labeled with tdTomato color. After 2mg/30g body weight tamoxifen injection, NG2tdT mice rested for 7 days followed by exposure to FiO2 10% for 21 days. The hypoxic and normoxic lung lobes were harvested and digested to single cell suspension using Collagenase and Dnase. From the single cell suspension, tdT positive cells were sorted and enriched using FACS and immediately loaded into the Chromium Single cell controller (10x Genomics). Single cell RNA-seq libraries were generated using 10X provided reagents.