Sin3a regulates epithelial progenitor cell fate during lung development

Yao, C, Carraro, G, Konda, B, Guan, X, Mizuno, T, Chiba, N, Kostelny, M, Kurkciyan, A, David, G, McQualter, J and Stripp, B 2017, 'Sin3a regulates epithelial progenitor cell fate during lung development', Development (Cambridge), vol. 144, no. 14, pp. 2618-2628.


Document type: Journal Article
Collection: Journal Articles

Title Sin3a regulates epithelial progenitor cell fate during lung development
Author(s) Yao, C
Carraro, G
Konda, B
Guan, X
Mizuno, T
Chiba, N
Kostelny, M
Kurkciyan, A
David, G
McQualter, J
Stripp, B
Year 2017
Journal name Development (Cambridge)
Volume number 144
Issue number 14
Start page 2618
End page 2628
Total pages 11
Publisher Company of Biologists Ltd
Abstract Mechanisms that regulate tissue-specific progenitors for maintenance and differentiation during development are poorly understood. Here, we demonstrate that the co-repressor protein Sin3a is crucial for lung endoderm development. Loss of Sin3a in mouse early foregut endoderm led to a specific and profound defect in lung development with lung buds failing to undergo branching morphogenesis and progressive atrophy of the proximal lung endoderm with complete epithelial loss at later stages of development. Consequently, neonatal pups died at birth due to respiratory insufficiency. Further analysis revealed that loss of Sin3a resulted in embryonic lung epithelial progenitor cells adopting a senescence-like state with permanent cell cycle arrest in G1 phase. This was mediated at least partially through upregulation of the cell cycle inhibitors Cdkn1a and Cdkn2c. At the same time, loss of endodermal Sin3a also disrupted cell differentiation of the mesoderm, suggesting aberrant epithelial-mesenchymal signaling. Together, these findings reveal that Sin3a is an essential regulator for early lung endoderm specification and differentiation.
Subject Cell Development, Proliferation and Death
Keyword(s) Epithelial-mesenchymal signaling
Foregut endoderm
G1 arrest
Mouse
P21/Cdkn1a
Progenitor cell fate
Sin3a
DOI - identifier 10.1242/dev.149708
Copyright notice © 2017. Published by The Company of Biologists Ltd.
ISSN 0950-1991
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