TY - JOUR
T1 - The in vivo genetic program of murine primordial lung epithelial progenitors
AU - Ikonomou, Laertis
AU - Herriges, Michael J.
AU - Lewandowski, Sara L.
AU - Marsland, Robert
AU - Villacorta-Martin, Carlos
AU - Caballero, Ignacio S.
AU - Frank, David B.
AU - Sanghrajka, Reeti M.
AU - Dame, Keri
AU - Kańduła, Maciej M.
AU - Hicks-Berthet, Julia
AU - Lawton, Matthew L.
AU - Christodoulou, Constantina
AU - Fabian, Attila J.
AU - Kolaczyk, Eric
AU - Varelas, Xaralabos
AU - Morrisey, Edward E.
AU - Shannon, John M.
AU - Mehta, Pankaj
AU - Kotton, Darrell N.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85078855153
U2 - 10.1038/s41467-020-14348-3
DO - 10.1038/s41467-020-14348-3
M3 - Article
C2 - 32005814
AN - SCOPUS:85078855153
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 635
ER -