Tissue Repair Postgraduate Training Programme

Shiau Haln Chen co-authors paper on single-cell RNA-seq of mouse endothelial cells in Pulmonary Arterial Hypertension

Tissue Repair PhD student Shiau Haln Chen is co-first author on a study showing distinct transcriptional profiles of endothelial subpopulations in Pulmonary Arterial Hypertension.

Shiau Haln Chen, who is undertaking her PhD research in the lab of Professor Andrew Baker at the Centre for Cardiovascular Sciences, has co-authored a paper based on her PhD work. The published study uses single-cell RNA-sequencing (scRNA-seq) to investigate transcriptional changes that mouse endothelial cells undergo in the disease Pulmonary Arterial Hypertension (PAH).

Endothelial cells drive the initiation and pathogenesis of PAH, but the heterogeneous nature of endothelial cells and the disease warranted further investigation into how different endothelial subpopulations respond. In the paper, Shiau Haln and colleagues report a global endothelial upregulation of the major histocompatibility complex class II (MHC-II) pathway, supporting a role for endothelial cells in the inflammatory response to the disease.

The authors also found a distinct response to PAH by one of the two capillary endothelial subpopulations. This subpopulation highly expressed genes involved in cell death, cell motility and angiogenesis. Using an in-silico cell ordering approach, they demonstrated zonation-dependent changes across the arteriovenous axis in PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and micro-vasculature.

Detailed analysis of rats and human whole-lung PAH scRNA-seq datasets further confirmed the relevance of these findings across different disease models and species, as 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. Overall, the study provides a high-resolution characterisation of endothelial responses to PAH, and highlights potential novel targets for the development of targeted therapeutics.

Rodor J, Chen SH et al. Single-cell RNA-seq profiling of mouse endothelial cells in response to pulmonary arterial hypertension. Cardiovascular Research 2021