Ceiling culture chip reveals dynamic lipid droplet transport during adipocyte dedifferentiation via actin remodeling

Abstract

Adipocyte dedifferentiation has recently gained attention as a process underpinning adipocyte plasticity; however, a lack of suitable experimental platforms has hampered studies into the underlying mechanisms. Here, we developed a...

ECM proteins and cationic polymers coating promote dedifferentiation of patient-derived mature adipocytes to stem cells

“…and TAZ regulation and pathways, 23,24,31 we can say that the confirmed expression of YAP in DFATs in our results (Fig. 2C) links the cell attachment and adhesion with the dedifferentiation process.…”

“…23,26,27 In the microfluidic system demonstrated by Kim et al, which provides the opportunity to observe the dedifferentiation mechanism in detail, it has been shown that actin myofibrils reorganize the cytoskeleton of the actin myofibrils and expel the lipid droplet from the cell, making the cells acquire a fibroblastic morphology while turning into DFATs. 24 This study also showed that coating with fibronectin on the surface promotes adipocyte dedifferentiation. Based on the related literature, we aimed to further control and improve the dedifferentiation ratio of mature adipocytes by using cationic and anionic polymers, and proteins which are the main components of the tissue extracellular matrix (ECM) and basement membrane (BM).…”

“…Thereby, the lipid secreting cell acquires a fibroblastic appearance by morphological rearrangements. According to current studies to explain the underlying mechanism mentioned that YAP/TAZ, 23 Hippo, Hedgehog signaling pathways 24 which are known to be involved in cytoskeletal remodeling, play a role in this process. It has also been shown on mesenchymal stem cells (MSCs) that as YAP expression increases, the cell geometry accordingly acquires a more elongated shape.…”

“…2A and B), as previously reported in the literature. 8,24 This process occurs by actin remodeling after mature adipocytes adhere to the surface, resulting in dynamic cellular deformation and secreting of the cell lipid droplet. Thereby, the lipid secreting cell acquires a fibroblastic appearance by morphological rearrangements.…”

“…20,22 In current studies investigating the chemical, biological and physiological factors underlying the mechanism of mature adipocyte dedifferentiation, it has been reported that the YAP/TAZ, Hippo, Hedgehog, and PPARγ signaling pathways play a role by reorganizing the cytoskeleton. 23,24 To date, various factors such as the oxygen content of the medium 25 and the stiffness of the substrate 23 have been emphasized in studies investigating the causes of dedifferentiation of mature adipocytes. Although the dedifferentiation mechanism within them has not been fully elucidated, several related reports have confirmed that substrate stiffness might be one of the important factors.…”