Evidence for myoblast-extrinsic regulation of slow myosin heavy chain expression during muscle fiber formation in embryonic development.
Evidence for myoblast-extrinsic regulation of slow myosin heavy chain expression during muscle fiber formation in embryonic development.
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在胚胎发育中肌肉纤维形成过程中肌球蛋白重链缓慢链表达缓慢的肌球蛋白重链表达的证据。
DOI：
10.1083/jcb.121.4.795
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发表时间：
1993-05
影响因子：
7.8
通讯作者：
Blau, H M
中科院分区：
文献类型：
--
作者：
Cho, M;Webster, S G;Blau, H M
脊椎动物的肌肉是由一系列不同的快和慢纤维类型与不同的收缩性能。纤维之间的差异，快速和缓慢的MyHC表达可能是由于外在因素，作用于分化的肌纤维。或者，融合形成多核肌纤维的单核成肌细胞可能由于谱系而本质上不同。为了区分这些可能性，我们确定了慢纤维比例的变化是否归因于成肌细胞的固有差异。表达慢肌球蛋白重链（MyHC）的纤维的比例被发现在胚胎和胎儿人肢体发育过程中随时间的变化显着。在前三个月，最多有75%的纤维表达慢型MyHC。此后，形成了不表达这种MyHC的新纤维，因此表达慢MyHC的纤维比例在妊娠中期下降到约3%。几周后，新纤维的一个子集开始表达慢MyHC，从妊娠30周到成年，大约50%的纤维是慢的。然而，每个成肌细胞克隆（n = 2，119）来源于人类发育六个阶段（妊娠第7、9、16和22周，出生后2个月和成年）的肌肉组织，在分化时表达缓慢的MyHC。我们得出结论，从这些结果，在胚胎发育过程中的肌纤维形成在体内缓慢的MyHC表达的控制在很大程度上是外在的成肌细胞。相比之下，来自相同样本的人类成肌细胞克隆在胚胎和新生儿MyHCs的表达方面存在差异，与其他物种的研究一致，并且这种差异被证明是稳定遗传的。即使在组织培养中进行25次群体倍增后，胚胎期成肌细胞也不能产生能够表达新生期典型MyHCs的成肌细胞，这表明阶段特异性差异不受分裂依赖性机制或内在“时钟”的控制。总而言之，这些结果表明，与胚胎和新生儿MyHC不同，在妊娠期间不同发育阶段体内缓慢MyHC的表达不是致力于不同成肌细胞谱系的结果，而是在很大程度上由环境决定。
Vertebrate muscles are composed of an array of diverse fast and slow fiber types with different contractile properties. Differences among fibers in fast and slow MyHC expression could be due to extrinsic factors that act on the differentiated myofibers. Alternatively, the mononucleate myoblasts that fuse to form multinucleated muscle fibers could differ intrinsically due to lineage. To distinguish between these possibilities, we determined whether the changes in proportion of slow fibers were attributable to inherent differences in myoblasts. The proportion of fibers expressing slow myosin heavy chain (MyHC) was found to change markedly with time during embryonic and fetal human limb development. During the first trimester, a maximum of 75% of fibers expressed slow MyHC. Thereafter, new fibers formed which did not express this MyHC, so that the proportion of fibers expressing slow MyHC dropped to approximately 3% of the total by midgestation. Several weeks later, a subset of the new fibers began to express slow MyHC and from week 30 of gestation through adulthood, approximately 50% of fibers were slow. However, each myoblast clone (n = 2,119) derived from muscle tissues at six stages of human development (weeks 7, 9, 16, and 22 of gestation, 2 mo after birth and adult) expressed slow MyHC upon differentiation. We conclude from these results that the control of slow MyHC expression in vivo during muscle fiber formation in embryonic development is largely extrinsic to the myoblast. By contrast, human myoblast clones from the same samples differed in their expression of embryonic and neonatal MyHCs, in agreement with studies in other species, and this difference was shown to be stably heritable. Even after 25 population doublings in tissue culture, embryonic stage myoblasts did not give rise to myoblasts capable of expressing MyHCs typical of neonatal stages, indicating that stage-specific differences are not under the control of a division dependent mechanism, or intrinsic "clock." Taken together, these results suggest that, unlike embryonic and neonatal MyHCs, the expression of slow MyHC in vivo at different developmental stages during gestation is not the result of commitment to a distinct myoblast lineage, but is largely determined by the environment.