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Dryad

Lung distal epithelium ChiaRed and WT epithelial cells

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Oct 16, 2024 version files 41.87 MB

Abstract

Using a method that enriches for alveolar epithelial cells, we compared distal epithelial cells from wild-type (WT) mice with AMCase reporter (ChiaRed; CR)-expressing epithelial cells from heterozygous CR mice by scRNAseq to further verify the cellular identity of AMCase-expressing cells. In the steady-state, EpCAM+ cells from WT mice were primarily comprised of mature AT2 (93%) and Tm4sf1-expressing alveolar epithelial progenitor cells (AEP; ~6%); AMCase-expressing CR+ cells matched the transcriptional profile of mature AT2s, as expected based on prior studies. In contrast to AT2s, AEPs were comparatively enriched for transcripts marking transitional alveolar epithelial cell states (Krt8, Krt19, Cldn4, Cdkn1a) that expand in pathological settings such as severe SARS-CoV-2 infection and pulmonary fibrosis. In addition, AEPs and AT2s differentially expressed Epcam, Cdh1, and H2-Ab1, encoding cell surface markers EpCAM, E-cadherin, and MHC-II, respectively, which were used to distinguish these populations by flow cytometry.