Dataset Information

SNEV^hPrp19/hPso4 Regulates Adipogenesis of Human Adipose Stromal Cells.

ABSTRACT: Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV^hPrp19/hPso4, which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differentiation and led to accumulation of DNA damage in hASCs upon oxidative stress. In addition, we demonstrated that SNEV is required for fat deposition in Caenorhabditis elegans. Consequently, we tested other DDR factors and found that WRN is also required for adipogenesis in both models. These results demonstrate that SNEV regulates adipogenesis in hASCs and indicate that DDR capacity in general might be a pre-requisite for this process.

SUBMITTER: Khan A

PROVIDER: S-EPMC5233435 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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SNEV<sup>hPrp19/hPso4</sup> Regulates Adipogenesis of Human Adipose Stromal Cells.

Khan Abdulhameed A Dellago Hanna H Terlecki-Zaniewicz Lucia L Karbiener Michael M Weilner Sylvia S Hildner Florian F Steininger Viktoria V Gabriel Christian C Mück Christoph C Jansen-Dürr Pidder P Hacobian Ara A Scheideler Marcel M Grillari-Voglauer Regina R Schosserer Markus M Grillari Johannes J

Stem cell reports 20161229 1

Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV<sup>hPrp19/hPso4</sup>, which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differe ...[more]

PMID: 28041875

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Project description:Introduction:Adipose-derived stromal/stem cells (ASCs) have attracted attention as a promising material for regenerative medicine. Previously, we reported an age-related decrease in the adipogenic potential of ASCs from human subjects and found that the individual difference in this potential increased with age, although the mechanisms remain unclear. Recently, other groups demonstrated that a secreted antagonist of bone morphogenetic protein (BMP) signaling, Gremlin 2 (GREM2), inhibits the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts and the adipogenesis of 3T3-L1 cell. Here, we examined the effects of GREM2 on the differentiation of ASCs into adipocytes. Methods:To examine changes in GREM2 expression levels with age, immunohistochemistry was performed on subcutaneous adipose tissues from subjects 12-97 years of age. Next, GREM2 gene expression levels in ASCs collected from subjects 5-90 years of age were examined by RT-PCR, and the change with age and correlation between the expression level and the adipogenic potential of ASCs were analyzed. In addition, to assess whether GREM2 affects adipogenesis, ASCs (purchased from a vendor) were cultured to induce adipogenesis with recombinant GREM2 protein, and siRNA-induced GREM2 knockdown experiment was also performed using aged ASCs. Results:In adipose tissues, GREM2 expression was observed in cells, including ASCs, but not in mature adipocytes, and the expression level per cell increased with age. GREM2 expression levels in ASCs cultured in vitro also increased with age, and the individual differences in the level increased with age. Of note, partial correlation analysis controlled for age revealed that the adipogenic potential of ASCs and the GREM2 gene expression level were negatively correlated. Furthermore, based on a GREM2 addition experiment, GREM2 has inhibitory effects on the adipogenesis of ASCs through activation of Wnt/?-catenin signaling. On the other hand, GREM2 knockdown in aged ASCs promoted adipogenesis. Conclusions:The GREM2 expression level was confirmed to play a role in the age-related decrease in adipogenic potential observed in ASCs isolated from adipose tissues as well as in the enhancement of the individual difference, which increased with age. GREM2 in adipose tissues increased with age, which suggested that GREM2 functions as an inhibitory factor of adipogenesis in ASCs.

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Dataset Information

SNEVhPrp19/hPso4 Regulates Adipogenesis of Human Adipose Stromal Cells.

Publications

SNEV<sup>hPrp19/hPso4</sup> Regulates Adipogenesis of Human Adipose Stromal Cells.

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SNEV^hPrp19/hPso4 Regulates Adipogenesis of Human Adipose Stromal Cells.