Hyperoxia prevents the dynamic neonatal increases in lung mesenchymal cell diversity

Abstract

Rapid expansion of the pulmonary microvasculature through angiogenesis drives alveolarization, the final stage of lung development that occurs postnatally and dramatically increases lung gas-exchange surface area. Disruption of pulmonary angiogenesis induces long-term structural and physiologic lung abnormalities, including bronchopulmonary dysplasia, a disease characterized by compromised alveolarization. Although endothelial cells are primary determinants of pulmonary angiogenesis, mesenchymal cells (MC) play a critical and dual role in angiogenesis and alveolarization. Therefore, we performed single cell transcriptomics and in-situ imaging of the developing lung to profile mesenchymal cells during alveolarization and in the context of lung injury. Specific mesenchymal cell subtypes were present at birth with increasing diversity during alveolarization even while expressing a distinct transcriptomic profile from more mature correlates. Hyperoxia arrested the transcriptomic progression of the MC, revealed differential cell subtype vulnerability with pericytes and myofibroblasts most affected, altered cell to cell communication, and led to the emergence of Acta1 expressing cells. These insights hold the promise of targeted treatment for neonatal lung disease, which remains a major cause of infant morbidity and mortality across the world.

Integration of hyperspectral imaging and transcriptomics from individual cells with HyperSeq

“…Single cell omics are accelerating our understanding of cell biology 1 , shedding light on new cell types and states in culture as well as in vivo across tissues, organs, and organisms [2][3][4][5] . While major breakthroughs have been achieved on increasing throughput of scRNA-Seq and related technologies to thousands [6][7][8][9] and sometimes millions 9,10 of cells and to integrate distinct omic modalities into a single experiment (e.g.…”