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  Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures

Gkatzis, K., Panza, P., Peruzzo, S., & Stainier, D. Y. R. (2021). Differentiation of mouse fetal lung alveolar progenitors in serum-free organotypic cultures. ELIFE, 10: e65811. doi:10.7554/eLife.65811; 10.7554/eLife.65811.sa1; 10.7554/eLife.65811.sa2.

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 Creators:
Gkatzis, Konstantinos1, Author              
Panza, Paolo1, Author              
Peruzzo, Sofia1, Author              
Stainier, Didier Y. R.1, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              

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Free keywords: CASEIN KINASE; STEM-CELLS; WNT; REGENERATION; EPITHELIUM; RENEWAL; ROLESLife Sciences & Biomedicine - Other Topics; organoids; lung alveolus; cell differentiation; lung development; tip progenitor; alveolar epithelial cell; Mouse;
 Abstract: Lung epithelial progenitors differentiate into alveolar type 1 (AT1) and type 2 (AT2) cells. These cells form the air-blood interface and secrete surfactant, respectively, and are essential for lung maturation and function. Current protocols to derive and culture alveolar cells do not faithfully recapitulate the architecture of the distal lung, which influences cell fate patterns in vivo. Here, we report serum-free conditions that allow for growth and differentiation of mouse distal lung epithelial progenitors. We find that Collagen I promotes the differentiation of flattened, polarized AT1 cells. Using these organoids, we performed a chemical screen to investigate WNT signaling in epithelial differentiation. We identify an association between Casein Kinase activity and maintenance of an AT2 expression signature; Casein Kinase inhibition leads to an increase in AT1/progenitor cell ratio. These organoids provide a simplified model of alveolar differentiation and constitute a scalable screening platform to identify and analyze cell differentiation mechanisms.

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Language(s): eng - English
 Dates: 2021-09-29
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: ELIFE
Source Genre: Journal
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Publ. Info: SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND : eLIFE SCIENCES PUBL LTD
Pages: - Volume / Issue: 10 Sequence Number: e65811 Start / End Page: - Identifier: ISSN: 2050-084X