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

Autor: Gkatzis, Konstantinos, Panza, Paolo, Peruzzo, Sofia, Stainier, Didier YR
Rok vydání: 2021
Předmět:
Transcription
Genetic
Mouse
Cellular differentiation
Culture Media
Serum-Free
Mice
0302 clinical medicine
Biology (General)
Wnt Signaling Pathway
Cells
Cultured
organoids
0303 health sciences
Stem Cells
General Neuroscience
Wnt signaling pathway
General Medicine
respiratory system
lung alveolus
Tools and Resources
Cell biology
medicine.anatomical_structure
Medicine
Casein kinase 1
Stem cell
Casein Kinases
Genetic Markers
QH301-705.5
Science
Cell fate determination
Biology
Collagen Type I
General Biochemistry
Genetics and Molecular Biology
Alveolar cells
03 medical and health sciences
medicine
Animals
Progenitor cell
alveolar epithelial cell
030304 developmental biology
lung development
Lung alveolus
General Immunology and Microbiology
Epithelial Cells
tip progenitor
Mice
Inbred C57BL
Pulmonary Alveoli
cell differentiation
030217 neurology & neurosurgery
Developmental Biology
Zdroj: eLife
eLife, Vol 10 (2021)
ISSN: 2050-084X
DOI: 10.7554/elife.65811
Popis: 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.
Databáze: OpenAIRE
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