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The functionally undefined Stac3 gene, predicted to encode a SH3 domain- and C1 domain-containing protein, was recently found to be specifically expressed in skeletal muscle and essential to normal skeletal muscle development and contraction. In this study we determined the potential role of Stac3 in myoblast proliferation and differentiation, two important steps of muscle development. Neither siRNA-mediated Stac3 knockdown nor plasmid-mediated Stac3 overexpression affected the proliferation of C2C12 myoblasts. Stac3 knockdown promoted the differentiation of C2C12 myoblasts into myotubes as evidenced by increased fusion index, increased number of nuclei per myotube, and increased mRNA and protein expression of myogenic markers including myogenin and myosin heavy chain. In contrast, Stac3 overexpression inhibited the differentiation of C2C12 myoblasts into myotubes as evidenced by decreased fusion index, decreased number of nuclei per myotube, and decreased mRNA and protein expression of myogenic markers. Compared to wild-type myoblasts, myoblasts from Stac3 knockout mouse embryos showed accelerated differentiation into myotubes in culture as evidenced by increased fusion index, increased number of nuclei per myotube, and increased mRNA expression of myogenic markers. Collectively, these data suggest an inhibitory role of endogenous Stac3 in myoblast differentiation. Myogenesis is a tightly controlled program; myofibers formed from prematurely differentiated myoblasts are dysfunctional. Thus, Stac3 may play a role in preventing precocious myoblast differentiation during skeletal muscle development. 相似文献
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The goal of this study was to identify novel factors that mediate skeletal muscle development or function. We began the study by searching the gene expression databases for genes that have no known functions but are preferentially expressed in skeletal muscle. This search led to the identification of the Src homology three (SH3) domain and cysteine rich (C1) domain 3 (Stac3) gene. We experimentally confirmed that Stac3 mRNA was predominantly expressed in skeletal muscle. We determined if Stac3 plays a role in skeletal muscle development or function by generating Stac3 knockout mice. All Stac3 homozygous mutant mice were found dead at birth, were never seen move, and had a curved body and dropping forelimbs. These mice had marked abnormalities in skeletal muscles throughout the body, including central location of myonuclei, decreased number but increased cross-sectional area of myofibers, decreased number and size of myofibrils, disarrayed myofibrils, and streaming Z-lines. These phenotypes demonstrate that the Stac3 gene plays a critical role in skeletal muscle development and function in mice. 相似文献
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Sairi Miyata Tomotaka Yada Natsuko Ishikawa Kazi Taheruzzaman Ryohei Hara Takashi Matsuzaki Akio Nishikawa 《In vitro cellular & developmental biology. Animal》2017,53(3):231-247
To understand the mechanism of muscle remodeling during Xenopus laevis metamorphosis, we examined the in vitro effect of insulin-like growth factor 1 (IGF-1) on growth and differentiation of three different-fate myogenic cell populations: tadpole tail, tadpole dorsal, and young adult leg muscle. IGF-1 promoted growth and differentiation of both tail and leg myogenic cells only under conditions where these cells could proliferate. Inhibition of cell proliferation by DNA synthesis inhibitor cytosine arabinoside completely canceled the IGF-1’s cell differentiation promotion, suggesting the possibility that IGF-1’s differentiation-promotion effect is an indirect effect via IGF-1’s cell proliferation promotion. IGF-1 promoted differentiation dose dependently with maximum effect at 100–500 ng/ml. RT-PCR analysis revealed the upregulation (11-fold) of ifg1 mRNA expression in developing limbs, suggesting that IGF-1 plays a role in promoting muscle differentiation during limb development. The combined effect of triiodo-l-thyronine (T3) and IGF-1 was also examined. In adult leg cells, IGF-1 promoted growth and differentiation irrespective of the presence of T3. In larval tail cells, cell count was 76% lower in the presence of T3, and IGF-1 did not promote proliferation and differentiation in T3-containing medium. In larval dorsal cells, cell count was also lower in the presence of T3, but IGF-1 enhanced proliferation and differentiation in T3-containing medium. This result is likely due to the presence among dorsal cells of both adult and larval types (1:1). Thus, IGF-1 affects only adult-type myogenic cells in the presence of T3 and helps accelerate dorsal muscle remodeling during metamorphosis. 相似文献
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The voltage-dependent calcium channel (VDCC) in skeletal muscle probably plays a key role in transducing membrane charge movement to the calcium release channel. We report here that the expression of VDCC α1 and α2 mRNAs is developmentally regulated in differentiating C2Cl2 myogenic cells. The α1 mRNA is not detectable in the myoblast form of C2Cl2 cells while its expression is induced 20-fold in differentiated myotubes. In contrast, the α2 mRNA is weakly expressed in myoblasts but is also induced upon myogenic differentiation. 相似文献
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We have investigated the synthesis and coding capacity of RNA isolated from cultures of differentiating Drosophila embryonic muscle cells. We find that following muscle cell fusion, the sedimentation profile of newly synthesized polyadenylated RNA becomes somewhat lighter. In vitro translation products analyzed by two-dimensional gel electrophoresis indicate that the coding capacity of translatable myogenic mRNA changes during differentiation. A group of several muscle-specific proteins (including the contractile proteins) is translated only from mRNA isolated after the initiation of fusion. This pattern coincides with proteins synthesized in vivo during differentiation. Additionally, we find that polyadenylated and nonpolyadenylated myogenic mRNA from a given developmental stage in culture have extremely similar coding potentials. 相似文献
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Amaresh C. Panda Kotb Abdelmohsen Jennifer L. Martindale Clara Di?Germanio Xiaoling Yang Ioannis Grammatikakis Ji Heon Noh Yongqing Zhang Elin Lehrmann Dawood B. Dudekula Supriyo De Kevin G. Becker Elizabeth J. White Gerald M. Wilson Rafael de?Cabo Myriam Gorospe 《Nucleic acids research》2016,44(5):2393-2408
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Wei Lv Wei Jiang Hongmei Luo Qian Tong Xiaoyu Niu Xiao Liu Yang Miao Jingnan Wang Yiwen Guo Jianan Li Xizhen Zhan Yunqing Hou Yaxin Peng Jian Wang Shuhong Zhao Zaiyan Xu Bo Zuo 《Nucleic acids research》2022,50(18):10733
Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration. 相似文献
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Background
The capacity of muscle to grow or to regenerate after damage is provided by adult stem cells, so called satellite cells, which are located under the basement lamina of each myofiber. Upon activation satellite cells enter the cell cycle, proliferate and differentiate into myoblasts, which fuse to injured myofibers or form new fibers. These processes are tightly controlled by many growth factors.Results
Here we investigate the role of bone morphogenetic proteins (BMPs) during satellite cell differentiation. Unlike the myogenic C2C12 cell line, primary satellite cells do not differentiate into osteoblasts upon BMP signaling. Instead BMP signaling inhibits myogenic differentiation of primary satellite cells ex vivo. In contrast, inhibition of BMP signaling results in cell cycle exit, followed by enhanced myoblast differentiation and myotube formation. Using an in vivo trauma model we demonstrate that satellite cells respond to BMP signals during the regeneration process. Interestingly, we found the BMP inhibitor Chordin upregulated in primary satellite cell cultures and in regenerating muscles. In both systems Chordin expression follows that of Myogenin, a marker for cells committed to differentiation.Conclusion
Our data indicate that BMP signaling plays a critical role in balancing proliferation and differentiation of activated satellite cells and their descendants. Initially, BMP signals maintain satellite cells descendants in a proliferating state thereby expanding cell numbers. After cells are committed to differentiate they upregulate the expression of the BMP inhibitor Chordin thereby supporting terminal differentiation and myotube formation in a negative feedback mechanism. 相似文献17.
A family of small proline-rich proteins (SPR1s) is induced in cells undergoing squamous differentiation. Because SPR1 mRNA is detected in mesenchymal nasal cells of rats exposed to cigarette smoke, expression of this mRNA in other nonsquamous cells and tissues was investigated. Using PCR, low levels of SPR1 mRNA were identified in a number of nondifferentiating cell lines and in nonsquamous tissues. G0SPR1 mRNA, the hamster homologue of SPR1 mRNA, was increased 10-fold in Chinese hamster ovary (CHO) cells when the culture reached 80–90% confluence and was downregulated after cells ceased growing at 100% confluence. The deduced amino acid sequence of G0SPR1 showed a high homology to the family of SPR1 from different species. Affinity-purified antibodies to SPR1 reacted to about 50% of the CHO cell population, indicating that the protein is expressed at specific stages of the cell cycle. CHO cells that were switched to low-serum medium when they were at 60% confluence showed an increase in G0SPR1 levels before the cells entered G0, indicating that G0SPR1 may be a signal to cells entering G0. Because expression of the SPR1 family of proteins is associated with squamous differentiation, the observations in the nondifferentiating CHO cells indicate that these proteins may play a role in mediating the withdrawal from the cell cycle prior to the commitment to differentiation. 相似文献
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《Experimental mycology》1989,13(1):105-108
The level of histone H4 mRNA was measured during spherulation and germination of Physarum polycephalum cultures. Histone H4 mRNA is present in prespherules as well as in mature and germinating spherules. During this differentiation process the cells have a 4C or G2-phase DNA content and therefore no DNA synthesis occurs. The presence of histone mRNA in the dormant cells shows that Physarum prepares long in advance for resumption of vegetative growth. 相似文献
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Kevin CR Kerr Sharon M Birks Mikhail V Kalyakin Yaroslav A Red'kin Eugeny A Koblik Paul DN Hebert 《Frontiers in zoology》2009,6(1):1-13