Expanding upon the critical advancements brought forth by single-cell omics in pulmonary hypertension (PH) research, this review delves deep into how these technologies have been piloted in a new era of understanding this complex disease. By leveraging the power of single-cell transcriptomics (i.e., single-cell RNA sequencing), researchers can now dissect the complicated cellular ecosystem of the lungs, examining the key players such as endothelial cells, smooth muscle cells, pericytes, and immune cells and their unique roles in the pathogenesis of PH. This more granular view is beyond the limitations of traditional bulk analysis, allowing for the identification of novel therapeutic targets previously obscured in the aggregated data. Connectome analysis based on single-cell omics of the cells involved in pathological changes can reveal a clearer picture of the cellular interactions and transitions in the cellular subtypes. Furthermore, the review acknowledges the challenges that lie ahead, including the need to enhance the resolution of single-cell RNA sequencing to capture even finer details of cellular changes, overcoming logistical barriers in processing human tissue samples, and the necessity of integrating diverse omics approaches to fully comprehend the molecular underpinnings of PH. The promise of these single-cell technologies is immense, offering the potential for targeted drug development and the discovery of biomarkers for early diagnosis and disease monitoring. Through these advancements, the field moves closer to realizing the goal of precision medicine for patients with PH.
Supported by American Heart Association grant 969574 (O.R.) and National Heart, Lung, and Blood Institute R01 grants HL132918 and HL151447 (R.R.), HL139664, HL160018, HL134776, and HL59886 (V.d.J.P.), HL133085 and HL160666, and HL166932 (T.V.K), HL133085 and HL160666 (O.R.).
Author Contributions: R.R., V.d.J.P., T.V.K., and O.R. wrote and edited the manuscript. A.D. analyzed single-cell data and edited the figure legends.
Originally Published in Press as DOI: 10.1165/rcmb.2024-0145PS on August 14, 2024
Author disclosures are available with the text of this article at www.atsjournals.org.