TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

Li, Shengnan; Wu, Jiafa

doi:10.1186/s13287-020-1552-y

Cited by 104 publications

(67 citation statements)

References 75 publications

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“…Transforming growth factor beta inhibits preadipocyte commitment through mothers against decapentaplegic 3 (SMAD3) signalling, by phosphorylating and suppressing PPARγ expression as well as the expression of C/EBPs [52,53]. Deletion of transforming growth factor beta receptor 2 (Tgfbr2) in MSCs resulted in a marked increase in adipocyte expansion in murine bone marrow and this was accompanied by an increase in PPARγ expression [54].…”

Section: Tgf-β Signallingmentioning

confidence: 99%

“…This complex is translocated to the nucleus to regulate BMP4 signalling to target genes such as translationally controlled tumour protein 1 (TPT1), lysyl oxidase (LOX) and αB-crystallin, which are involved in the commitment of C3H10T1/2 cells to the adipocyte lineage [56]. BMP4 treated C3H10T1/2 cells differentiated into adipocytes with increased expression of C/EBPα, PPARγ, and adipocyte protein 2 (aP2) [53]. BMP4 pre-treated C3H10T1/2 cells implanted subcutaneously into athymic mice developed into adipose tissue similar to that found in normal fat depots [57].…”

Section: Bmp Signallingmentioning

confidence: 99%

“…Treatment of A33 preadipocytes derived from C3H10T1/2 cells with the BMP4 antagonist noggin, inhibited adipogenic differentiation, indicating the importance of BMP4 in maintaining preadipocyte commitment [58]. Inhibiting BMP4 signalling in human adipose derived stromal/stem cells (hASCs) suppresses adipogenesis [53]. Adipose precursor cells secrete Wnt1 inducible signalling pathway protein (WISP2) which forms a complex with zinc finger protein 423 (Zfp423) in the absence of BMP4 stimulation.…”

Section: Bmp Signallingmentioning

confidence: 99%

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Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Ambele

Dhanraj

Giles

2020

IJMS

165

110

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The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.

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Section: Tgf-β Signallingmentioning

confidence: 99%

Section: Bmp Signallingmentioning

confidence: 99%

Section: Bmp Signallingmentioning

confidence: 99%

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Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Ambele

Dhanraj

Giles

2020

IJMS

165

110

View full text Add to dashboard Cite

show abstract

“…The abundance of vWAT exosomes were found to be negatively correlated with BMI in teenage girls [50]. Among those differentially expressed miRNAs in vWAT between obese and lean girls, the majority are involved in TGF-β and Wnt/β-catenin signaling pathways, which regulate adipogenesis and inflammatory responses [51,52]. In morbidly obese men, plasma miR-130b, which promotes adipose tissue inflammation and insulin resistance [53], and miR-423-5p, which promotes angiogenesis [54], were decreased [55].…”

Section: Adipokines Lipokines and Endocrine Disruption In Obesitymentioning

confidence: 99%

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

2020

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In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.

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“…In addition to WNT signaling pathway, NOTCH signaling, TGF-beta signaling and FGF signaling pathways were also identified. They are all important pathways regulating MSC self-renewal and differentiation [47][48][49]. The interactive molecules of the pathways among clusters identified here could guide future studies investigating the regulatory mechanisms of eMSC differentiation.…”

Section: Discussionmentioning

confidence: 79%

Revealing Cellular Heterogeneity and In Vitro Differentiation Trajectory of Cultured Human Endometrial Mesenchymal-like Stem Cells Using Single-cell RNA Sequencing

Cao¹,

Chan

et al. 2020

Preprint

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Endometrial mesenchymal-like stem cells (eMSCs) are adult stem cells contributing to endometrial regeneration. One set of perivascular markers (CD140b + CD146 + ) have been widely used to enrich eMSCs. Although eMSCs are easily accessible for regenerative medicine and have long been studied, their cellular heterogeneity and molecular program controlling their expansion and differentiation in vitro remains largely unclear. In this study, we applied 10X genomics single-cell RNA sequencing to eMSCs cultured in vitro after microbeading from 7 donors to investigate cellular heterogeneity in an unbiased manner. Corresponding clonogenic progenies of eMSCs after culture for 14 days were also sequenced to construct the in vitro differentiation trajectory of eMSCs. Transcriptomic expression based clustering revealed several subpopulations in eMSCs. Each subpopulation manifested distinct functional characteristics associated with immunomodulation, proliferation, extracellular matrix organization and cell differentiation. Pseudotime trajectory analysis on eMSCs and their differentiated progenies identified in vitro differentiation hierarchy of eMSCs. Further ligand-receptor pair analysis found that WNT signaling, NOTCH signaling, TGF-beta signaling and FGF signaling were important regulatory pathways for eMSC self-renewal and differentiation. By comparing eMSCs to Wharton's Jelly MSCs and adipose-derived MSCs, we found these 3 kinds of MSCs expressed largely overlapping differentiation (CD) genes and highly variable genes. In summary, we reveal for the first time high molecular and cellular heterogeneity in cultured eMSCs, and identify the key signaling pathways that may be important for eMSC differentiation.

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TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

Cited by 104 publications

References 75 publications

Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

Revealing Cellular Heterogeneity and In Vitro Differentiation Trajectory of Cultured Human Endometrial Mesenchymal-like Stem Cells Using Single-cell RNA Sequencing

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