Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture
Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture
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DOI：
10.1002/jcp.10016
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发表时间：
2001-11-01
影响因子：
5.6
通讯作者：
Wold, B
中科院分区：
文献类型：
--
作者：
Csete, M;Walikonis, J;Wold, B
干细胞生物学中的主要问题围绕着定义细胞群的发育潜力和理解它们的潜力是如何维持或逐渐限制的。氧（O-2）是骨骼肌前体细胞培养过程中一个重要的环境因素，但在骨骼肌前体细胞的培养过程中却很少受到关注。在这项工作中，我们研究了O-2水平对成人骨骼肌纤维祖细胞群（卫星细胞）的发育潜力，增殖能力和表型的影响，以及骨骼肌发育的多潜能胚胎近轴中胚层模型细胞系。卫星细胞增殖和成熟纤维的存活率在生理性（6%）O-2中比在几乎所有传统细胞培养中使用的非生理性20%O-2中增加。6%的O-2条件也加速了多种MyoD家族肌生成调节因子（MRF）的上调。一个意想不到的发现是，纤维粘附卫星细胞可以承担非肌原性表型。通过分子标记物和总脂质积累的标准，卫星细胞被发现承担脂肪细胞表型，并在20%O-2比生理O-2更显着。选择的脂肪形成的命运和执行的脂肪形成的多潜能间充质细胞系也显着较高，在传统的20与6%的O-2，和减少脂肪形成的生理O-2与显着减少表达的脂肪形成调节剂，过氧化物酶体增殖物激活受体γ。这些结果表明，受O-2的调节途径是重要的卫星细胞增殖，执行细胞的命运，和父母的肌肉在文化中的生存，因此可能在体内正常或病理条件下发挥作用。(C)2001 Wiley-Liss，Inc.
Major problems in stem cell biology revolve around defining the developmental potential of cell populations and understanding how their potential is maintained or progressively restricted. Oxygen (O-2) is an obvious environmental factor which has received little attention in culturing skeletal muscle progenitor cells. In this work, we examine the effects of O-2 levels on the developmental potential, proliferative capacity, and phenotype of the adult skeletal muscle fiber progenitor population (satellite cells), and cell lines that model multipotential embryonic paraxial mesoderm from which skeletal muscle develops. Both satellite cell proliferation and survival of mature fibers increased in physiologic (6%) O-2 vs non-physiologic 20% O-2 used in virtually all traditional cell culture. Six percent O-2 conditions also accelerated the up-regulation of multiple MyoD family myogenic regulatory factors (MRFs). An unexpected finding was that fiber-adherent satellite cells could assume a non-myogenic phenotype. By the criteria of molecular markers and gross lipid accumulation, satellite cells were found to assume an adipocyte phenotype, and did so more prominently in 20% O-2 than in physiologic O-2. Selection of the adipogenic fate and execution of adipogenesis by multipotential mesenchymal cell lines was also dramatically higher in traditional 20 vs. 6% O-2, and decreased adipogenesis in physiologic O-2 was associated with significantly less expression of the adipogenic regulator, PPAR gamma. These results suggest that regulatory pathways affected by O-2 are important for satellite cell proliferation, execution of cell fate, and parent muscle survival in culture, and so may play a role in vivo under normal or pathologic conditions. (C) 2001 Wiley-Liss, Inc.