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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage
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BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage

机译：BMP信号传导通路是C3H10T1 / 2多能干细胞进入脂肪细胞谱系的必需条件

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摘要

Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3H10T1/2 pluripotent stem cells into adipocytes. After treatment of C3H10T1/2 stem cells with these BMPs during proliferation followed by exposure to differentiation inducers at growth arrest, nearly all cells enter the adipose development pathway, express specific adipocyte markers, and acquire the adipocyte phenotype. Overexpression of constitutively active BMP receptor (CA)-BMPr1A or CA-BMPr1B induces commitment in the absence of BMP2/4, whereas overexpression of a dominant-negative receptor dominant-negative-BMPr1A suppresses commitment induced by BMP. Also, knockdown of the expression of Smad4 (coregulator in the BMP/Smad signaling pathway) with RNAi disrupts commitment by the BMPs. However, knockdown of expression of p38 MAPK (an intermediary in the BMP/MAPK signaling pathway) with RNAi had little effect on BMP-induced commitment. Together, these findings indicate that the BMP/Smad signaling pathway has a dominant role in adipocyte lineage determination. Proteomic analysis identified lysyl oxidase (LOX), a bona fide downstream target gene of the BMP signaling pathway. Expression of LOX is induced by BMP2/4 during adipocyte lineage commitment, and knockdown of its expression disrupts the commitment process.
机译：肥胖伴随着脂肪细胞数量和大小的增加。脂肪细胞数量的增加是脂肪组织血管基质中存在的多能干细胞向脂肪细胞谱系募集的结果。这些多能细胞具有进行定型然后分化为脂肪细胞以及肌细胞，骨细胞和软骨细胞的潜力。在本文中，我们表明，骨形态发生蛋白（BMP）2和BMP4均可诱导C3H10T1 / 2多能干细胞向脂肪细胞的定向转移。在增殖过程中用这些BMP处理C3H10T1 / 2干细胞后，在生长停滞时暴露于分化诱导剂后，几乎所有细胞进入脂肪发育途径，表达特定的脂肪细胞标志物，并获得脂肪细胞表型。组成性活性BMP受体（CA）-BMPr1A或CA-BMPr1B的过表达在没有BMP2 / 4的情况下诱导承诺，而显性-负受体的主-负-BMPr1A的过度表达抑制BMP诱导的承诺。同样，用RNAi抑制Smad4（BMP / Smad信号通路中的调节剂）的表达会破坏BMP的作用。然而，RNAi抑制p38 MAPK表达（BMP / MAPK信号传导途径的中介）对BMP诱导的承诺几乎没有影响。在一起，这些发现表明BMP / Smad信号通路在脂肪细胞谱系确定中起主导作用。蛋白质组学分析确定了赖氨酰氧化酶（LOX），BMP信号传导途径的真正下游靶基因。在脂肪细胞谱系定型过程中，LOX的表达是由BMP2 / 4诱导的，其敲低会破坏定型过程。

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  • 作者

    Haiyan Huang; Tan-Jing Song; Xi Li; Lingling Hu; Qun He; Mei Liu; M. Daniel Lane; Qi-Qun Tang;

  • 作者单位

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China;

    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

    Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    lysyl oxidase; preadipocyte; Smad4; adipogenesis; differentiation;

    机译：赖氨酰氧化酶;前脂肪细胞Smad4;脂肪形成差异化;

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