Distinct roles for Notch1 and Notch3 in human adipose-derived stem/stromal cell adipogenesis
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ORIGINAL ARTICLE
Distinct roles for Notch1 and Notch3 in human adipose‑derived stem/ stromal cell adipogenesis Meng‑Cheng Liu1 · Hannah Logan1 · Jamie J. Newman1 Received: 16 June 2020 / Accepted: 30 September 2020 © Springer Nature B.V. 2020
Abstract The role of the Notch signaling pathway in adipogenesis has long been controversial as the action of individual Notch receptors appears to vary with experimental conditions. In this study, we offer some explanation for the observed contradictions by comparing the role of both Notch1 and Notch3 in regulating the expression of key adipogenic regulator, PPARγ, in human adipose-derived stem/stromal cells (hADSCs) during in vitro adipogenesis. Utilizing qRT-PCR, western blot, and immunofluorescence staining, we demonstrated that Notch3 was expressed prior to the formation of lipid vesicles, while Notch1 only appeared after vesicle formation. In addition, following the induction of adipogenesis, the levels of Notch1 intracellular domain in the nucleus were significantly reduced, while the siRNA-mediated loss of Notch1 reduced transcript but not protein levels of PPARγ. The knockdown of Notch3 led to increased expression of PPARγ during early adipogenesis that was not paralleled by a decreased expression of Hes1 and Hey1, but was accompanied by a marked decrease in the protein level of β-catenin, the key functional component of the canonical Wnt/β-catenin signaling pathway. This study deepens the understanding of the Notch pathway by clarifying the distinct roles of Notch1 and Notch3 during adipogenesis. We showed that Notch3 is involved in early adipogenic differentiation, while Notch1 functions later in the process. In addition, we begin to uncover the interaction between the Notch and Wnt signaling pathways that may offer novel therapeutic targets aimed at obesity and diabetes. Keywords Notch1 · Notch3 · Wnt · Adipogenesis · hADSC
Introduction Obesity and obesity-related diseases are an ever-growing health concern. The symptoms associated with obesity are in part related to the formation and accumulation of adipose tissue that leads to inflammation and alters metabolism [1]. In order to better understand how obesity contributes to compounding health concerns and identify potential therapeutic targets to curb these downstream affects, there must be further investigation of the mechanistic process that drives and regulates adipogenesis. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05884-8) contains supplementary material, which is available to authorized users. * Jamie J. Newman [email protected] 1
School of Biological Sciences, Louisiana Tech University, Ruston, LA 71272, USA
The increase in adipocytes in adults depends on the rate and regulation of adipogenesis of both precursors and human adipose-derived stem/stromal cells (hADSCs). hADSCs are a type of mesenchymal stem cell with the ability to selfrenew and differentiate into multiple types of cells from the mesoderm germ layer [2]. Continuous r
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