Mironov, A., Fisher, M., Narayanan, P. et al. (3 more authors) (2023) Rac1 controls cell turnover and reversibility of the involution process in postpartum mammary glands. PLOS Biology, 21 (1). e3001583. ISSN 1544-9173
Abstract
Cell turnover in adult tissues is essential for maintaining tissue homeostasis over a life span and for inducing the morphological changes associated with the reproductive cycle. However, the underlying mechanisms that coordinate the balance of cell death and proliferation remain unsolved. Using the mammary gland, we have discovered that Rac1 acts as a nexus to control cell turnover. Postlactational tissue regression is characterised by the death of milk secreting alveoli, but the process is reversible within the first 48 h if feeding recommences. In mice lacking epithelial Rac1, alveolar regression was delayed. This defect did not result from failed cell death but rather increased cell turnover. Fitter progenitor cells inappropriately divided, regenerating the alveoli, but cell death also concomitantly accelerated. We discovered that progenitor cell hyperproliferation was linked to nonautonomous effects of Rac1 deletion on the macrophageal niche with heightened inflammation. Moreover, loss of Rac1 impaired cell death with autophagy but switched the cell death route to apoptosis. Finally, mammary gland reversibility failed in the absence of Rac1 as the alveoli failed to recommence lactation upon resuckling.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2023 Mironov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Mammary glands; Apoptosis; Autophagic cell death; Lactation; Milk; Inflammation; Cell death; Adipocytes |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 200588/Z/16/Z MEDICAL RESEARCH COUNCIL MR/P028411/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Jan 2023 12:39 |
Last Modified: | 24 Jan 2023 12:39 |
Published Version: | http://dx.doi.org/10.1371/journal.pbio.3001583 |
Status: | Published |
Publisher: | Public Library of Science (PLoS) |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pbio.3001583 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:195570 |