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The in vivo genetic program of murine primordial lung epithelial progenitors

Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors...

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Detalles Bibliográficos
Autores principales: Ikonomou, Laertis, Herriges, Michael J., Lewandowski, Sara L., Marsland, Robert, Villacorta-Martin, Carlos, Caballero, Ignacio S., Frank, David B., Sanghrajka, Reeti M., Dame, Keri, Kańduła, Maciej M., Hicks-Berthet, Julia, Lawton, Matthew L., Christodoulou, Constantina, Fabian, Attila J., Kolaczyk, Eric, Varelas, Xaralabos, Morrisey, Edward E., Shannon, John M., Mehta, Pankaj, Kotton, Darrell N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994558/
https://www.ncbi.nlm.nih.gov/pubmed/32005814
http://dx.doi.org/10.1038/s41467-020-14348-3
Descripción
Sumario:Multipotent Nkx2-1-positive lung epithelial primordial progenitors of the foregut endoderm are thought to be the developmental precursors to all adult lung epithelial lineages. However, little is known about the global transcriptomic programs or gene networks that regulate these gateway progenitors in vivo. Here we use bulk RNA-sequencing to describe the unique genetic program of in vivo murine lung primordial progenitors and computationally identify signaling pathways, such as Wnt and Tgf-β superfamily pathways, that are involved in their cell-fate determination from pre-specified embryonic foregut. We integrate this information in computational models to generate in vitro engineered lung primordial progenitors from mouse pluripotent stem cells, improving the fidelity of the resulting cells through unbiased, easy-to-interpret similarity scores and modulation of cell culture conditions, including substratum elastic modulus and extracellular matrix composition. The methodology proposed here can have wide applicability to the in vitro derivation of bona fide tissue progenitors of all germ layers.