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Publication : The in vivo genetic program of murine primordial lung epithelial progenitors.

First Author  Ikonomou L Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  635
PubMed ID  32005814 Mgi Jnum  J:356259
Mgi Id  MGI:7762351 Doi  10.1038/s41467-020-14348-3
Citation  Ikonomou L, et al. (2020) The in vivo genetic program of murine primordial lung epithelial progenitors. Nat Commun 11(1):635
abstractText  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-beta 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.
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