Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin.
Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin.
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DOI：
10.1083/jcb.200511036
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发表时间：
2006-10-09
期刊：
影响因子：
--
通讯作者：
Gussoni E
中科院分区：
文献类型：
--
作者：
Frank NY;Kho AT;Schatton T;Murphy GF;Molloy MJ;Zhan Q;Ramoni MF;Frank MH;Kohane IS;Gussoni E
骨骼肌侧群(SP)细胞被认为是“干细胞”样细胞。尽管有报道证实肌肉SP细胞在体外和体内都能产生分化的后代，但其表型的分子机制仍不清楚。本研究通过对人胎儿骨骼肌基因表达的分析，发现骨形态发生蛋白4(BMP4)在SP细胞中高表达，但在主要群体(MP)单核肌源性细胞中不表达。功能研究表明，BMP4特异性地诱导BMP受体1a阳性的MP细胞增殖，但对BMPR1A阴性的SP细胞无影响。相比之下，BMP4拮抗剂Gremlin在MP细胞中特异性上调，抵消了BMP4的刺激作用，并抑制了BMPR1A阳性肌肉细胞的增殖。在活体内，BMP4阳性细胞位于BMPR1A阳性细胞附近的肌纤维间间隙。Gremlin由成熟的肌纤维和间质细胞表达，它们独立于表达BMP4的细胞。综上所述，这些研究表明，BMP4和Gremlin分别在人胎儿骨骼肌SP和MP细胞中高表达，是肌源性祖细胞增殖的调节因子。
Skeletal muscle side population (SP) cells are thought to be “stem”-like cells. Despite reports confirming the ability of muscle SP cells to give rise to differentiated progeny in vitro and in vivo, the molecular mechanisms defining their phenotype remain unclear. In this study, gene expression analyses of human fetal skeletal muscle demonstrate that bone morphogenetic protein 4 (BMP4) is highly expressed in SP cells but not in main population (MP) mononuclear muscle-derived cells. Functional studies revealed that BMP4 specifically induces proliferation of BMP receptor 1a–positive MP cells but has no effect on SP cells, which are BMPR1a-negative. In contrast, the BMP4 antagonist Gremlin, specifically up-regulated in MP cells, counteracts the stimulatory effects of BMP4 and inhibits proliferation of BMPR1a-positive muscle cells. In vivo, BMP4-positive cells can be found in the proximity of BMPR1a-positive cells in the interstitial spaces between myofibers. Gremlin is expressed by mature myofibers and interstitial cells, which are separate from BMP4-expressing cells. Together, these studies propose that BMP4 and Gremlin, which are highly expressed by human fetal skeletal muscle SP and MP cells, respectively, are regulators of myogenic progenitor proliferation.
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影响因子：
7.8
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
通讯作者：
Rudnicki, Michael A
影响因子：
4.6
作者：
Dahlqvist, C;Blokzijl, A;Lendahl, U
通讯作者：
Lendahl, U
影响因子：
2.7
作者：
Cornelison, DDW;Olwin, BB;Wold, BJ
通讯作者：
Wold, BJ
DOI：
10.1016/s0006-291x(02)00828-8
发表时间：
2002-08-02
影响因子：
3.1
作者：
Chen, B;Athanasiou, M;Blair, DG
通讯作者：
Blair, DG
影响因子：
30.8
作者：
BYERS, TJ;LIDOV, HGW;KUNKEL, LM
通讯作者：
KUNKEL, LM