Dataset Information

Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/?-catenin Signaling Pathway.

ABSTRACT: Increased adipocytes are associated with obesity and many human disorders including cancers. To further understand the molecular mechanisms of adipogenesis, transcriptome sequencing was performed to find genes involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). The mRNA of taurine transporter (TauT, also known as SLC6A6) was found significantly upregulated in hASCs undergoing differentiation. TauT expression was also markedly increased in fat tissues from obese mice induced by high fat diet or genetic mutations (ob/ob and db/db mice). In vitro, downregulation of TauT attenuated effectively the adipogenic differentiation of hASCs, and TauT overexpression promoted the formation of adipocytes. Among the molecules transported by TauT, hypotaurine and ?-alanine promoted adipocyte formation, whereas taurine inhibited the process. Moreover, the inhibitory effect of TauT knockdown on hASCs differentiation was largely reversed by hypotaurine and ?-alanine through promoting the downregulation of ?-catenin. These results indicated that TauT regulate adipocyte formation through transported amino acids and may serve as a target for therapeutic intervention of obesity.

SUBMITTER: Hou X

PROVIDER: S-EPMC6535786 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/β-catenin Signaling Pathway.

Hou Xiaodan X Wang Zhixue Z Ding Fang F He Yang Y Wang Pengyuan P Liu Xia X Xu Feng F Wang Jun J Yang Yili Y

International journal of biological sciences 20190422 5

Increased adipocytes are associated with obesity and many human disorders including cancers. To further understand the molecular mechanisms of adipogenesis, transcriptome sequencing was performed to find genes involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). The mRNA of taurine transporter (TauT, also known as SLC6A6) was found significantly upregulated in hASCs undergoing differentiation. TauT expression was also markedly increased in fat tissues from obes ...[more]

PMID: 31182929

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Project description:BackgroundGEM (GTP-binding protein overexpressed in skeletal muscle) is one of the atypical small GTPase subfamily members recently identified as a regulator of cell differentiation. Abnormal chondrogenesis coupled with an imbalance in the turnover of cartilaginous matrix formation is highly relevant to the onset and progression of osteoarthritis (OA). However, how GEM regulates chondrogenic differentiation remains unexplored.MethodsCartilage tissues were obtained from OA patients and graded according to the ORASI and ICRS grading systems. The expression alteration of GEM was detected in the Grade 4 cartilage compared to Grade 0 and verified in OA mimic culture systems. Next, to investigate the specific function of GEM during these processes, we generated a Gem knockdown (Gem-Kd) system by transfecting siRNA targeting Gem into ATDC5 cells. Acan, Col2a1, Sox9, and Wnt target genes of Gem-Kd ATDC5 cells were detected during induction. The transcriptomic sequencing analysis was performed to investigate the mechanism of GEM regulation. Wnt signaling pathways were verified by real-time PCR and immunoblot analysis. Finally, a rescue model generated by treating Gem-KD ATDC5 cells with a Wnt signaling agonist was established to validate the mechanism identified by RNA sequencing analysis.ResultsA decreased expression of GEM in OA patients' cartilage tissues and OA mimic chondrocytes was observed. While during chondrogenesis differentiation and cartilage matrix formation, the expression of GEM was increased. Gem silencing suppressed chondrogenic differentiation and the expressions of Acan, Col2a1, and Sox9. RNA sequencing analysis revealed that Wnt signaling was downregulated in Gem-Kd cells. Decreased expression of Wnt signaling associated genes and the total β-CATENIN in the nucleus and cytoplasm were observed. The exogenous Wnt activation exhibited reversed effect on Gem loss-of-function cells.ConclusionThese findings collectively validated that GEM functions as a novel regulator mediating chondrogenic differentiation and cartilage matrix formation through Wnt/β-catenin signaling.

Project description:BackgroundObesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and differentiation. The objective of the present study was to identify and investigate the function and regulatory mechanism of lncRNAs on adipogenic differentiation of hADSCs.MethodsWe used lncRNA arrays to identify the prominent differentially expressed lncRNAs before and after hADSC adipogenic differentiation and verified their biological function through antisense oligonucleotide knockdown or lentivirus overexpression. The adipogenic differentiation of hADSCs was assessed by oil red O staining as well as the mRNA and protein levels of adipogenic marker genes through qRT-PCR and western blot. Bioinformatic tool LncPro and immunofluorescence was performed to uncover the interaction between lnc13728 and ZBED3. WNT/β-catenin signaling pathway was evaluated by western blot and immunofluorescence.ResultsThe lncRNA arrays showed that lnc13728 expression was significantly upregulated after hADSC adipogenic differentiation and was correlated positively with the expression of the adipogenesis-related genes in human adipose tissue. Lnc13728 knockdown in hADSCs suppressed the expression of the adipogenesis-related genes at both mRNA and protein level and weakened lipid droplet production. Accordingly, lnc13728 overexpression enhanced hADSC adipogenic differentiation. Beyond that, lnc13728 co-localized with ZBED3 in the cytoplasm and regulated its expression positively. Downregulating ZBED3 had a negative effect on adipogenic differentiation, while the expression of WNT/β-catenin signaling pathway-related proteins was upregulated.ConclusionsLnc13728 promotes hADSC adipogenic differentiation possibly by positively regulating the expression of ZBED3 which plays a role in inhibiting the WNT/β-catenin pathway.

Dataset Information

Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/?-catenin Signaling Pathway.

Publications

Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/β-catenin Signaling Pathway.

Similar Datasets

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