Genome-wide effect of pulmonary airway epithelial cell–specific Bmal1 deletion

CD3 antigen; Arntl protein, mouse; Article; RNA sequence; C57BL mouse; Alveolar Epithelial Cells; Animals; ARNTL Transcription Factors; Cells, Cultured; Circadian Clocks; Female; Gene Deletion; Humans; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; Transcriptome; Xenobiotics

Abstract :

[en] Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of the circadian clock using mice bearing targeted deletion of the circadian gene brain and muscle ARNT-like 1 (Bmal1) in AECs. Pulmonary neutrophil infiltration, biomechanical function, and responses to influenza infection were all disrupted. A circadian time-series RNA sequencing study of laser-captured AECs revealed widespread disruption in genes of the core circadian clock and output pathways regulating cell metabolism (lipids and xenobiotics), extracellular matrix, and chemokine signaling, but strikingly also the gain of a novel rhythmic transcriptome in Bmal1-targeted cells. Many of the rhythmic components were replicated in primary AECs cultured in air-liquid interface, indicating significant cell autonomy for control of pulmonary circadian physiology. Finally, we found that metabolic cues dictate phasing of the pulmonary clock and circadian responses to immunologic challenges. Thus, the local circadian clock in AECs is vital in lung health by coordinating major cell processes such as metabolism and immunity.—Zhang, Z. Hunter, L., Wu, G., Maidstone, R., Mizoro, Y., Vonslow, R., Fife, M., Hopwood, T., Begley, N., Saer, B., Wang, P., Cunningham, P., Baxter, M., Durrington, H., Blaikley, J. F., Hussell, T., Rattray, M., Hogenesch, J. B., Gibbs, J., Ray, D. W., Loudon, A. S. I. Genome-wide effect of pulmonary airway epithelial cell-specific Bmal1 deletion. FASEB J. 33, 6226–6238 (2019). www.fasebj.org. © FASEB

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Zhang, Z.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Hunter, L.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Wu, G.; Cincinnati Children's Hospital Medical Center > Center for Chronobiology > Division of Human Genetics

Maidstone, R.; University of Manchester > Division of Informatics, Imaging, and Data Sciences

Mizoro, Yasutaka ; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Vonslow, R.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Fife, M.; University of Manchester > Faculty of Biology, Health, and Medicine > Manchester Center for Collaborative Inflammation Research

Hopwood, T.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Begley, N.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

Saer, B.; University of Manchester > Faculty of Biology, Health, and Medicine > Centre for Biological Timing

More authors (11 more)

Language :

English

Title :

Genome-wide effect of pulmonary airway epithelial cell–specific Bmal1 deletion

Publication date :

May 2019

Journal title :

FASEB Journal

ISSN :

0892-6638

eISSN :

1530-6860

Publisher :

John Wiley and Sons Inc.

Volume :

Issue :

Pages :

6226-6238

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 03 June 2020

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