The Role of Cellular Proliferation in Adipogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells

Abstract

Mitotic clonal expansion has been suggested as a prerequisite for adipogenesis in murine preadipocytes, but the precise role of cell proliferation during human adipogenesis is unclear. Using adipose tissue-derived human mesenchymal stem cells as an in vitro cell model for adipogenic study, a group of cell cycle regulators, including Cdk1 and CCND1, were found to be downregulated as early as 24 h after adipogenic initiation and consistently, cell proliferation activity was restricted to the first 48 h of adipogenic induction. Cell proliferation was either further inhibited using siRNAs targeting cell cycle genes or enhanced by supplementing exogenous growth factor, basic fibroblast growth factor (bFGF), at specific time intervals during adipogenesis. Expression knockdown of Cdk1 at the initiation of adipogenic induction resulted in significantly increased adipocytes, even though total number of cells was significantly reduced compared to siControl-treated cells. bFGF stimulated proliferation throughout adipogenic differentiation, but exerted differential effect on adipogenic outcome at different phases, promoting adipogenesis during mitotic phase (first 48 h), but significantly inhibiting adipogenesis during adipogenic commitment phase (days 3-6). Our results demonstrate that cellular proliferation is counteractive to adipogenic commitment in human adipogenesis. However, cellular proliferation stimulation can be beneficial for adipogenesis during the mitotic phase by increasing the population of cells capable of committing to adipocytes before adipogenic commitment.

A genome-wide landscape of mRNAs, lncRNAs, and circRNAs during subcutaneous adipogenesis in pigs

“…Besides, these two markers have been found to be involved in growth arrest of differentiation [ 30 , 31 ]. Before preadipocyte differentiation, growth arrest is a necessary process for blocking the cell in the G 1 phase [ 32 , 33 ]; restricted cell proliferation has been found to appear at D2 of differentiation in human mesenchymal stem cells [ 32 , 34 ]. In the G 1 /S phase, CDK1 , CCND1 , and E2F1 have been shown to play a key role in regulating the cell cycle [ 35 ].…”

“…In the G 1 /S phase, CDK1 , CCND1 , and E2F1 have been shown to play a key role in regulating the cell cycle [ 35 ]. Furthermore, the expression of CDK1 and CCND1 decreased at the early stage of differentiation in human and porcine preadipocytes [ 34 , 36 ]. Additionally, PPARG has been reported to control the cell cycle by decreasing the activity of E2F and CCND1 and upregulating the expression of cyclin-dependent kinase inhibitors [ 30 , 37 , 38 ], while CEBPA can repress the expression of E2F1 , which results in the impairment of the ability of cell differentiation, and simultaneously suppresses cell proliferation [ 31 ].…”

Effect of Optimized Concentrations of Basic Fibroblast Growth Factor and Epidermal Growth Factor on Proliferation of Fibroblasts and Expression of Collagen

“…The culture medium was replaced with fibroblast-inducing medium containing 20 ng/ml bFGF (Gibco) and 20 ng/ml EGF (Gibco), and then ADSCs were cultured to 40–50% confluence. [ 15 16 ] Cells were cultured for another 2 weeks, and the medium was changed every 2–3 days. The cells were then identified by flow cytometry and immunohistochemistry.…”

Identification of potential biomarkers or therapeutic targets of mesenchymal stem cells in multiple myeloma by bioinformatics analysis

“…Besides, previous studies also showed that the downregulation of CDK1 was related to osteogenic differentiation disorder and senescence of MSCs [22][23][24]. In addition, it was interesting that expression knockdown of CDK1 resulted in significantly increased adipogenic differentiation of AD-MSCs [25]. Therefore, abnormal expression of CDK1 in MSCs may also result in dysfunction of MSCs and lead to progression of MM although further functional studies are still needed.…”