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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cellular Biochemistry
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1547836
Exploring the role of cell cycle regulation in human mature adipocyte dedifferentiation
Provisionally accepted
Giada Ostinelli1,2Marie-Frédérique Gauthier2Nathalie Vernoux3
Emilie Bernier1,2Tristan Dubé1,2Simon Marceau2Stephane Lebel2
Marie-Ève Tremblay4
Andre Tchernof1,2*- 1Laval University, Quebec, Canada
- 2Research Center of the University Institute of Cardiology and Respirology of Quebec, Laval University, Quebec City, Quebec, Canada
- 3Centre de Recherche du CHU de Québec, Québec City, Quebec, Canada
- 4Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
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Background: Dedifferentiated fat (DFAT) cells have been used in regenerative medicine thanks to their multipotent potential. According to the literature, the process of adipocyte dedifferentiation is characterized by liposecretion and increased expression of genes related to cell cycle, which results in a fibroblast-like, proliferating cell population. A number of pathways have been implicated in the process, but the role of the cell cycle in adipocyte dedifferentiation has yet to be investigated. Here we characterize the process of liposecretion, the cellular features of DFAT cells and the role of the cell cycle.Methods: Primary adipocytes and adipocyte-derived pluripotent cells (APC) were isolated from humanadipose tissue and mature adipocytes were dedifferentiated in ceiling culture. The intracellular organization of DFAT and APC were compared using transmission electron microscopy (TEM), and the changes of intracellular lipid content over time were tracked with Oil-Red O. Finally, we tested whether liposecretion is a cell cycle-dependent phenomenon by cultivating mature adipocytes in ceiling culture with or without four different inhibitors of the cell cycle (AraC, Irinotecan, Vincristine and RO-3306).Results: DFAT cells are enriched in intracellular lipids, which are stored in small lipid droplets.In addition, liposecretion, which characterizes mature adipocyte dedifferentiation, is characterized by the rapid secretion of a large lipid droplet that is coated by a membrane. This phenomenon seems to be hindered by the presence of cyclin dependent kinase 1 (CDK1) inhibitor RO-3306.Both human adipose tissues depots undergo dedifferentiation in vitro, but visceral adipose tissue DFAT retain more lipids than subcutaneous-derived DFAT. Liposecretion is characterized by the rapid ejection of a membrane-wrapped lipid droplet. This phenomenon is dependent on CDK1 and likely relies on the presence of integrin-mediated cellular adherence.
Keywords: dedifferentiation, Dedifferentiated fat cells (DFAT cells)2, DFAT, liposecretion, Cell Cycle
Received: 18 Dec 2024; Accepted: 14 Apr 2025.
Copyright: © 2025 Ostinelli, Gauthier, Vernoux, Bernier, Dubé, Marceau, Lebel, Tremblay and Tchernof. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andre Tchernof, Laval University, Quebec, Canada
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