The in vivo genetic program of murine primordial lung epithelial progenitors.
Animals
Cell Culture Techniques
Cell Differentiation
Epithelial Cells
/ cytology
Extracellular Matrix
/ genetics
Female
Germ Layers
/ embryology
Lung
/ cytology
Male
Mice
/ embryology
Mice, Inbred C57BL
Mice, Transgenic
Pluripotent Stem Cells
/ cytology
Signal Transduction
Thyroid Nuclear Factor 1
/ genetics
Transcriptome
Transforming Growth Factor beta
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 01 2020
31 01 2020
Historique:
received:
20
05
2019
accepted:
23
12
2019
entrez:
2
2
2020
pubmed:
2
2
2020
medline:
12
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32005814
doi: 10.1038/s41467-020-14348-3
pii: 10.1038/s41467-020-14348-3
pmc: PMC6994558
doi:
Substances chimiques
Nkx2-1 protein, mouse
0
Thyroid Nuclear Factor 1
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
635Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL128172
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR001810
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119461
Pays : United States
Organisme : NHLBI NIH HHS
ID : R24 HL123828
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105029
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL124280
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001410
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007035
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134745
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122096
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL095993
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL111574
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122442
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001430
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL134766
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL140129
Pays : United States
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