First Author | Alber AB | Year | 2023 |
Journal | Nat Commun | Volume | 14 |
Issue | 1 | Pages | 3488 |
PubMed ID | 37311756 | Mgi Jnum | J:340977 |
Mgi Id | MGI:7491157 | Doi | 10.1038/s41467-023-39099-9 |
Citation | Alber AB, et al. (2023) Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme. Nat Commun 14(1):3488 |
abstractText | While the generation of many lineages from pluripotent stem cells has resulted in basic discoveries and clinical trials, the derivation of tissue-specific mesenchyme via directed differentiation has markedly lagged. The derivation of lung-specific mesenchyme is particularly important since this tissue plays crucial roles in lung development and disease. Here we generate a mouse induced pluripotent stem cell (iPSC) line carrying a lung-specific mesenchymal reporter/lineage tracer. We identify the pathways (RA and Shh) necessary to specify lung mesenchyme and find that mouse iPSC-derived lung mesenchyme (iLM) expresses key molecular and functional features of primary developing lung mesenchyme. iLM recombined with engineered lung epithelial progenitors self-organizes into 3D organoids with juxtaposed layers of epithelium and mesenchyme. Co-culture increases yield of lung epithelial progenitors and impacts epithelial and mesenchymal differentiation programs, suggesting functional crosstalk. Our iPSC-derived population thus provides an inexhaustible source of cells for studying lung development, modeling diseases, and developing therapeutics. |