iPSC-derived and primary lung alveolar type 2 cells
Updated February 2, 2024Dysfunction of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, is implicated in pulmonary disease pathogenesis, highlighting the importance of human in vitro models. However, AEC2-like cells in culture have yet to be directly compared to their in vivo counterparts at single-cell resolution. Here, we performed head-to-head comparisons among the transcriptomes of primary adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell–derived AEC2s (iAEC2s). We found each population occupied a distinct transcriptomic space with cultured AEC2s (primary and iAEC2s) exhibiting similarities to and differences from freshly purified primary cells. Across each cell type, we found an inverse relationship between proliferative and maturation states, with preculture primary AEC2s being most quiescent/mature and iAEC2s being most proliferative/least mature. Cultures of either type of human AEC2s did not generate detectable alveolar type 1 cells in these defined conditions; however, a subset of iAEC2s cocultured with fibroblasts acquired a transitional cell state described in mice and humans to arise during fibrosis or following injury. Hence, we provide direct comparisons of the transcriptomic programs of primary and engineered AEC2s, 2 in vitro models that can be harnessed to study human lung health and disease.
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Analysis Portals
NoneProject Label
iPSC-derived and primary lung alveolar type 2 cellsSpecies
Sample Type
Anatomical Entity
Organ Part
Selected Cell Types
Disease Status (Specimen)
Disease Status (Donor)
Development Stage
Library Construction Method
Nucleic Acid Source
Paired End
falseAnalysis Protocol
1a58aa2b-297a-464b-8d6c-470b6e0e2b1aFile Format
Cell Count Estimate
UnspecifiedDonor Count
3