Ostinelli Giada, Gauthier Marie-Frédérique, Vernoux Nathalie, Bernier Emilie, Dubé Tristan, Marceau Simon, Lebel Stéfane, Tremblay Marie-Ève, Tchernof André
Institut Universitaire de Cardiologie et Pneumologie de Québec-Université Laval, Québec, QC, Canada.
École de Nutrition, Université Laval, Québec, QC, Canada.
Front Cell Dev Biol. 2025 May 8;13:1547836. doi: 10.3389/fcell.2025.1547836. eCollection 2025.
Dedifferentiated fat (DFAT) cells have been used in regenerative medicine due to their multipotent potential. According to the literature, the process of adipocyte dedifferentiation is characterized by liposecretion which results in a fibroblastlike, proliferating cell population, with increased expression of genes related to cell cycle. 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.
Primary adipocytes and adipocyte-derived pluripotent cells (APC) were isolated from human adipose 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).
DFAT cells were 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 tissue depots undergo dedifferentiation , but visceral adipose tissue DFAT cells retain more lipids than subcutaneous-derived DFAT cells. 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.
去分化脂肪（DFAT）细胞因其多能性已被应用于再生医学。根据文献，脂肪细胞去分化过程的特征是脂滴分泌，这导致了成纤维细胞样的增殖细胞群，细胞周期相关基因的表达增加。该过程涉及多种途径，但细胞周期在脂肪细胞去分化中的作用尚未得到研究。在此，我们描述了脂滴分泌过程、DFAT细胞的细胞特征以及细胞周期的作用。
从人脂肪组织中分离出原代脂肪细胞和脂肪细胞来源的多能细胞（APC），并在悬滴培养中使成熟脂肪细胞去分化。使用透射电子显微镜（TEM）比较DFAT和APC的细胞内结构，并用油红O追踪细胞内脂质含量随时间的变化。最后，我们通过在有无四种不同细胞周期抑制剂（阿糖胞苷、伊立替康、长春新碱和RO - 3306）的悬滴培养中培养成熟脂肪细胞，来测试脂滴分泌是否是一种细胞周期依赖性现象。
DFAT细胞富含细胞内脂质，这些脂质储存于小脂滴中。此外，脂滴分泌是成熟脂肪细胞去分化的特征，其特点是一个被膜包裹的大脂滴快速分泌。这种现象似乎受到细胞周期蛋白依赖性激酶1（CDK1）抑制剂RO - 3306的抑制。
人脂肪组织库均会发生去分化，但内脏脂肪组织的DFAT细胞比皮下来源的DFAT细胞保留更多脂质。脂滴分泌的特征是一个被膜包裹的脂滴快速排出。这种现象依赖于CDK1，可能依赖于整合素介导的细胞黏附的存在。
