[HTML][HTML] Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme

AB Alber, HA Marquez, L Ma, G Kwong… - Nature …, 2023 - nature.com
AB Alber, HA Marquez, L Ma, G Kwong, BR Thapa, C Villacorta-Martin, J Lindstrom-Vautrin…
Nature Communications, 2023nature.com
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 …
Abstract
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.
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