MYOD CONVERTS PRIMARY DERMAL FIBROBLASTS, CHONDROBLASTS, SMOOTH-MUSCLE, AND RETINAL PIGMENTED EPITHELIAL-CELLS INTO STRIATED MONONUCLEATED MYOBLASTS AND MULTINUCLEATED MYOTUBES
MYOD CONVERTS PRIMARY DERMAL FIBROBLASTS, CHONDROBLASTS, SMOOTH-MUSCLE, AND RETINAL PIGMENTED EPITHELIAL-CELLS INTO STRIATED MONONUCLEATED MYOBLASTS AND MULTINUCLEATED MYOTUBES
复制标题
DOI：
10.1073/pnas.87.20.7988
复制
发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
HOLTZER, H
中科院分区：
文献类型：
--
作者：
CHOI, J;COSTA, ML;HOLTZER, H
在它们出生后不久，肌瘤、肢芽和常规肌肉培养中的有丝分裂后单核成肌细胞拉长并将一组肌原纤维蛋白组装成明确的条纹肌原纤维。MyoD诱导大量永生化和/或转化的非肌肉细胞表达结蛋白和几种肌原纤维蛋白，并融合成肌浆细胞。我们现在报道，MyoD将正常的真皮成纤维细胞、软骨母细胞、肌胃平滑肌和着色的视网膜上皮细胞转化为有丝分裂后的单核横纹肌母细胞。抗结蛋白、α-肌动蛋白、肌动蛋白、肌钙蛋白-I、α-肌动蛋白、肌球蛋白重链和肌球蛋白的抗体在这些转化的成肌细胞中的肌节定位与体内和体外的正常成肌细胞没有区别。转化后的成肌细胞融合成典型的各向异性多核肌管，通常自发收缩。骨骼肌生肌程序的转化和随后的表达是自主的事件，发生在四个非肌肉微环境中，由不同的前瞻蛋白细胞外基质分子组合组成。与MyoD转化相关的早期事件包括：(I)退出细胞周期，(Ii)被破坏的细胞“下调”S正在进行的分化程序，以及(Iii)在假定的成肌细胞中开始合成结蛋白，并在有丝分裂后的成肌细胞中显著地重新分布微管和结蛋白中间丝。
Shortly after their birth, postmitotic mononucleated myoblasts in myotomes, limb buds, and conventional muscle cultures elongate and assemble a cohort of myofibrillar proteins into definitively striated myofibrils. MyoD induces a number of immortalized and/or transformed nonmuscle cells to express desmin and several myofibrillar proteins and to fuse into myosacs. We now report that MyoD converts normal dermal fibroblasts, chondroblasts, gizzard smooth muscle, and pigmented retinal epithelial cells into elongated postmitotic mononucleated striated myoblasts. The sarcomeric localization of antibodies to desmin, .alpha.-actinin, titin, troponin-I, .alpha.-actin, myosin heavy chain, and myomesin in these converted myoblasts are indistinguishable from in vivo and in vitro normal myoblasts. Converted myoblasts fuse into typical anisodiametric multinucleated myotubes that often contract spontaneously. Conversion and subsequent expression of the skeletal myogenic program are autonomous events, occurring in four nonmuscle microenvironments consisting of different combinations of foregin extracellular matrix molecules. Early events associated with conversion by MyoD involve (i) withdrawal from the cell cycle, (ii) down-regulation of the subverted cell''s ongoing differentiation program, and (iii) initiation of desmin synthesis in presumptive myoblasts and dramatic redistribution of microtubules and desmin intermediate filaments in postmitotic myoblasts.