Claire L Burgess, Jessie Huang, Pushpinder S Bawa, Konstantinos-Dionysios Alysandratos, Kasey Minakin, Lauren J Ayers, Michael P Morley, Apoorva Babu, Carlos Villacorta-Martin, Maria Yampolskaya, Anne Hinds, Bibek R Thapa, Feiya Wang, Adeline Matschulat, Pankaj Mehta, Edward E Morrisey, Xaralabos Varelas, Darrell N Kotton
Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs...
April 15, 2024: Cell Stem Cell