modeling-dysplastic-functional-lung-alveolar-repair-after-influenza

Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection

Viral infection causes both acute and long-term damage to the lung alveolus, the specialized tissue structure responsible for gas exchange between the ...

National Institutes of Health

Endothelial cells (ECs) develop organ-specific gene expression and function in response to signals from the surrounding tissue. In turn, ECs can affect organ development and morphogenesis and promote or hinder disease response. In the lung, ECs play an essential role in gas exchange with the external environment, requiring both a close physical connection and a strong axis of communication with alveolar epithelial cells. A complete picture of the composition of the pulmonary endothelium is therefore critical for a full understanding of development, maintenance, and repair of the gas exchange interface. Defining the factors that control lung-specific EC specification, establish EC heterogeneity within the lung, and promote the differing contributions of EC subtypes to development, health, and disease will facilitate the development of much-needed regenerative therapies. This includes targeting therapeutics directly to ECs, developing pluripotent or primary cell-derived ECs to replace damaged or diseased vasculature, and vascularizing engineered tissues for transplant.

Specialized Pulmonary Vascular Cells in Development and Disease.

Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation. These cell states include an injury-induced capillary endothelial cell (iCAP) that arises after injury, persists indefinitely, and shares hallmarks with developing lung endothelium and endothelial aberrations found in degenerative human lung diseases. This dataset provides a foundational resource to understand the complexity of cellular and molecular responses to injury and correlations to responses found in human development and disease.

Article	Year
Specialized Pulmonary Vascular Cells in Development and Disease. Annual review of physiology\| PubMed ID: 39322434	2025
Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states. Cell stem cell\| PubMed ID: 39818203	2025

Arnav Sharma

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