Rac1 controls cell turnover and reversibility of the involution process in postpartum mammary glands

Aleksandr Mironov, Matthew Fisher, Priya Narayanan, Randa Elsayed, Melis Karabulutoglu, Nasreen Akhtar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


AU Cell:turnover Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.

Original languageEnglish
Article numbere3001583
JournalPLoS Biology
Issue number1
Publication statusPublished - Jan 2023
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Thomas, Berry and Simpson Fellowship (to NA), Wellcome Trust (#200588/Z/16/Z to NA) and Medical Research Council (MR/P028411/1 to NA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
Copyright: © 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.


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