The in vivo genetic program of murine primordial lung epithelial progenitors

Laertis Ikonomou (), Michael J. Herriges, Sara L. Lewandowski, Robert Marsland, Carlos Villacorta-Martin, Ignacio S. Caballero, David B. Frank, Reeti M. Sanghrajka, Keri Dame, Maciej M. Kańduła, Julia Hicks-Berthet, Matthew L. Lawton, Constantina Christodoulou, Attila J. Fabian, Eric Kolaczyk, Xaralabos Varelas, Edward E. Morrisey, John M. Shannon, Pankaj Mehta and Darrell N. Kotton ()
Additional contact information
Laertis Ikonomou: Boston University and Boston Medical Center
Michael J. Herriges: Boston University and Boston Medical Center
Sara L. Lewandowski: Boston University and Boston Medical Center
Robert Marsland: Boston University
Carlos Villacorta-Martin: Boston University and Boston Medical Center
Ignacio S. Caballero: Boston University and Boston Medical Center
David B. Frank: The Children’s Hospital of Philadelphia
Reeti M. Sanghrajka: Boston University and Boston Medical Center
Keri Dame: Boston University and Boston Medical Center
Maciej M. Kańduła: Boston University
Julia Hicks-Berthet: Boston University School of Medicine
Matthew L. Lawton: Boston University and Boston Medical Center
Constantina Christodoulou: Boston University School of Medicine
Attila J. Fabian: Biogen Inc.
Eric Kolaczyk: Boston University
Xaralabos Varelas: Boston University School of Medicine
Edward E. Morrisey: University of Pennsylvania
John M. Shannon: Division of Pulmonary Biology, Cincinnati Children’s Hospital
Pankaj Mehta: Boston University
Darrell N. Kotton: Boston University and Boston Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14348-3

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DOI: 10.1038/s41467-020-14348-3

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