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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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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
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author 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.
author_facet 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.
author_sort Ikonomou, Laertis
collection PubMed
description 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.
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spelling pubmed-69945582020-02-03 The in vivo genetic program of murine primordial lung epithelial progenitors 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. Nat Commun Article 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. Nature Publishing Group UK 2020-01-31 /pmc/articles/PMC6994558/ /pubmed/32005814 http://dx.doi.org/10.1038/s41467-020-14348-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
The in vivo genetic program of murine primordial lung epithelial progenitors
title The in vivo genetic program of murine primordial lung epithelial progenitors
title_full The in vivo genetic program of murine primordial lung epithelial progenitors
title_fullStr The in vivo genetic program of murine primordial lung epithelial progenitors
title_full_unstemmed The in vivo genetic program of murine primordial lung epithelial progenitors
title_short The in vivo genetic program of murine primordial lung epithelial progenitors
title_sort in vivo genetic program of murine primordial lung epithelial progenitors
topic Article
url 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
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