Notch3 is involved in adipogenesis of human adipose-derived stromal/stem cells

Sandel, Demi; Liu, Mengcheng; Ogbonnaya, Ngozi; Newman, Jamie J.

doi:10.1016/j.biochi.2018.04.020

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…6). Notch3 expression is also reported to be upregulated during adipogenesis (Sandel et al, 2018), however, silencing of Notch3 in that study did not decrease adipogenesis. The observed decrease in Notch3 could thus also be a consequence rather than a cause of the defect in adipogenesis.…”

Section: Discussioncontrasting

confidence: 53%

“…Since Notch3 was recently (Sandel et al, 2018) identified to play a role in adipogenesis and CDK6 is known to regulate Notch3 (Pekkonen et al, 2014), it was of interest to analyze whether the expression of Notch3 and its targets were affected. The expression of Notch3 and its target Hes1 were significantly downregulated in miR-107 transfected preadipocytes compared to NT, as demonstrated by western blotting (Fig.…”

Section: Notch3 and Its Target Gene Hes1 Expression Is Downregulated mentioning

confidence: 99%

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miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

Ahonen

Haridas

Mysore

et al. 2019

Molecular and Cellular Endocrinology

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MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in preand mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.

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Section: Discussioncontrasting

confidence: 53%

Section: Notch3 and Its Target Gene Hes1 Expression Is Downregulated mentioning

confidence: 99%

miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

Ahonen

Haridas

Mysore

et al. 2019

Molecular and Cellular Endocrinology

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“…Our experiments demonstrated that Notch3 silence promoted adipogenic differentiation ability in ADSCs. The results were consistent with a recent experiment, which also indicated that Notch3 was involved in adipogenesis of hADSCs [25]. Previous study demonstrated that a γ -secretase inhibitor of Notch signaling could increase the adipogenesis of mouse ADSCs by promotion of PPAR- γ expression [26].…”

Section: Discussionsupporting

confidence: 92%

MicroRNA-150 Modulates Adipogenic Differentiation of Adipose-Derived Stem Cells by Targeting Notch3

et al. 2019

Stem Cells International

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MicroRNAs (miRNAs) influence stem cell functions, including mobilization, proliferation, and differentiation. miR-150 is abundantly expressed in monocytes. Knockdown of miR-150 promotes bone marrow stem cell migration. The role of miR-150 in adipose-derived stem cells (ADSCs) is unclear. In this study, the effects of miR-150 on adipogenic differentiation and proliferation of ADSCs were investigated. ADSCs were isolated from the inguinal adipose tissue of wild-type (WT) and miR-150 knockout (KO) mice and were induced for adipogenic differentiation. The miR-150 level was detected by real-time PCR. ADSCs were transfected by miR-150 or small-interfering RNA (siRNA) of Notch3. MTT assay and colony formation assay were performed in miR-150 knockdown and control ADSCs. Real-time PCR showed that miR-150 was expressed in ADSCs. miR-150 knockdown significantly decreased the capacity of adipogenic differentiation of ADSCs, as compared with their counterparts from WT mice. It is intriguing that the overexpression of miR-150 significantly increased C/EBPα and PPAR-γ expression and lipid formation in ADSCs with adipogenic induction. Overexpression of miR-150 significantly decreased Notch3 expression in ADSCs compared with the control groups. Furthermore, Notch3 inhibition promoted the adipogenic differentiation in ADSCs. miR-150 also suppressed proliferation potential and the expression of Nanog in ADSCs. In summary, this study demonstrates, for the first time, that miR-150 promotes adipogenic differentiation and inhibits proliferation of ADSCs. miR-150 regulates adipogenic differentiation of ADSCs, likely mediated by the downregulation of Notch3.

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“…angiogenesis [53,54]. In general, despite only a few previous evidences support an implication of the Notch3 gene in obesity molecular pathways [55], the findings presented in this paper seem to point this TF as an important element for the proper regulation of AT cellular responses to WL. For investigating the sequential rules discovered in the VLCD group (Fig 4), the use of other biological quality measures instead of TF (such as BP and MF) allowed experts to identify several interesting patterns.…”

Section: Plos Computational Biologymentioning

confidence: 47%

eXplainable Artificial Intelligence (XAI) for the identification of biologically relevant gene expression patterns in longitudinal human studies, insights from obesity research

et al. 2020

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Until date, several machine learning approaches have been proposed for the dynamic modeling of temporal omics data. Although they have yielded impressive results in terms of model accuracy and predictive ability, most of these applications are based on "Black-box" algorithms and more interpretable models have been claimed by the research community. The recent eXplainable Artificial Intelligence (XAI) revolution offers a solution for this issue, were rule-based approaches are highly suitable for explanatory purposes. The further integration of the data mining process along with functional-annotation and pathway analyses is an additional way towards more explanatory and biologically soundness models. In this paper, we present a novel rule-based XAI strategy (including pre-processing, knowledgeextraction and functional validation) for finding biologically relevant sequential patterns from longitudinal human gene expression data (GED). To illustrate the performance of our pipeline, we work on in vivo temporal GED collected within the course of a long-term dietary intervention in 57 subjects with obesity (GSE77962). As validation populations, we employ three independent datasets following the same experimental design. As a result, we validate primarily extracted gene patterns and prove the goodness of our strategy for the mining of biologically relevant gene-gene temporal relations. Our whole pipeline has been gathered under open-source software and could be easily extended to other human temporal GED applications.

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Notch3 is involved in adipogenesis of human adipose-derived stromal/stem cells

Cited by 14 publications

References 31 publications

miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

miR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

MicroRNA-150 Modulates Adipogenic Differentiation of Adipose-Derived Stem Cells by Targeting Notch3

eXplainable Artificial Intelligence (XAI) for the identification of biologically relevant gene expression patterns in longitudinal human studies, insights from obesity research

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