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71.
Akihito Tanaka Knut Woltjen Katsuya Miyake Akitsu Hotta Makoto Ikeya Takuya Yamamoto Tokiko Nishino Emi Shoji Atsuko Sehara-Fujisawa Yasuko Manabe Nobuharu Fujii Kazunori Hanaoka Takumi Era Satoshi Yamashita Ken-ichi Isobe En Kimura Hidetoshi Sakurai 《PloS one》2013,8(4)
The establishment of human induced pluripotent stem cells (hiPSCs) has enabled the production of in vitro, patient-specific cell models of human disease. In vitro recreation of disease pathology from patient-derived hiPSCs depends on efficient differentiation protocols producing relevant adult cell types. However, myogenic differentiation of hiPSCs has faced obstacles, namely, low efficiency and/or poor reproducibility. Here, we report the rapid, efficient, and reproducible differentiation of hiPSCs into mature myocytes. We demonstrated that inducible expression of myogenic differentiation1 (MYOD1) in immature hiPSCs for at least 5 days drives cells along the myogenic lineage, with efficiencies reaching 70–90%. Myogenic differentiation driven by MYOD1 occurred even in immature, almost completely undifferentiated hiPSCs, without mesodermal transition. Myocytes induced in this manner reach maturity within 2 weeks of differentiation as assessed by marker gene expression and functional properties, including in vitro and in vivo cell fusion and twitching in response to electrical stimulation. Miyoshi Myopathy (MM) is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in DYSFERLIN. Using our induced differentiation technique, we successfully recreated the pathological condition of MM in vitro, demonstrating defective membrane repair in hiPSC-derived myotubes from an MM patient and phenotypic rescue by expression of full-length DYSFERLIN (DYSF). These findings not only facilitate the pathological investigation of MM, but could potentially be applied in modeling of other human muscular diseases by using patient-derived hiPSCs. 相似文献
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Furochi H Tamura S Mameoka M Yamada C Ogawa T Hirasaka K Okumura Y Imagawa T Oguri S Ishidoh K Kishi K Higashiyama S Nikawa T 《FEBS letters》2007,581(30):5743-5750
Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts. 相似文献
75.
This protocol details a method for monitoring glucose uptake into single, living mammalian cells using a fluorescent D-glucose derivative, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), as a tracer. The specifically designed chamber and superfusion system for evaluating 2-NBDG uptake into cells in real time can be combined with other fluorescent methods such as Ca2+ imaging and the subsequent immunofluorescent classification of cells exhibiting divergent 2-NBDG uptake. The whole protocol, including immunocytochemistry, can be completed within 2 d (except for cell culture). The procedure for 2-NBDG synthesis is also presented. 相似文献
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Rho-kinase--mediated contraction of isolated stress fibers 总被引:12,自引:0,他引:12
Katoh K Kano Y Amano M Onishi H Kaibuchi K Fujiwara K 《The Journal of cell biology》2001,153(3):569-584
It is widely accepted that actin filaments and the conventional double-headed myosin interact to generate force for many types of nonmuscle cell motility, and that this interaction occurs when the myosin regulatory light chain (MLC) is phosphorylated by MLC kinase (MLCK) together with calmodulin and Ca(2+). However, recent studies indicate that Rho-kinase is also involved in regulating the smooth muscle and nonmuscle cell contractility. We have recently isolated reactivatable stress fibers from cultured cells and established them as a model system for actomyosin-based contraction in nonmuscle cells. Here, using isolated stress fibers, we show that Rho-kinase mediates MLC phosphorylation and their contraction in the absence of Ca(2+). More rapid and extensive stress fiber contraction was induced by MLCK than was by Rho-kinase. When the activity of Rho-kinase but not MLCK was inhibited, cells not only lost their stress fibers and focal adhesions but also appeared to lose cytoplasmic tension. Our study suggests that actomyosin-based nonmuscle contractility is regulated by two kinase systems: the Ca(2+)-dependent MLCK and the Rho-kinase systems. We propose that Ca(2+) is used to generate rapid contraction, whereas Rho-kinase plays a major role in maintaining sustained contraction in cells. 相似文献
79.
We examined the effects of photoperiod on pituitary levels of two types of gonadotropin (GTH), GTH I and GTH II, in masu salmon Oncorhynchus masou to study their mechanism of synthesis. In Experiment 1, the effects of long or short photoperiod combined with castration were examined using 8-month-old precocious males. Castration was carried out in early August and then the fish were reared under a short (8L16D) or long (16L8D) photoperiod for 60 days. In Experiment 2, the effects of photoperiod combined with testosterone treatment were examined using 12-month-old immature females. Silastic tubes containing testosterone (500 microg /fish) or vehicle were implanted intra-peritoneally in early October. Fish were reared under 16L8D for 60 days, and then half of the fish were transferred to 8L16D, while the remaining fish were kept under 16L8D until Day 90. In Experiment 1, GTH I contents were higher under 16L8D than under 8L16D in the castrated group on Day 30. Moreover, GTH I contents were higher in the castrated group than the control group under 16L8D on Day 30. GTH II contents increased with testicular maturation in the control groups, whereas they remained at low levels in the castrated groups regardless of photoperiodic treatment. In Experiment 2, GTH I contents did not change remarkably in all the groups, while GTH II contents were remarkably increased by testosterone treatment regardless of photoperiodic treatment. These results indicate that the synthesis of GTH I and GTH II are differently regulated by photoperiod and testosterone in masu salmon. 相似文献
80.
Contribution of neurons to habituation to mechanical stimulation in Caenorhabditis elegans 总被引:1,自引:0,他引:1
In Caenorhabditis elegans, a light touch induces a locomotor response. Repeated touches, however, result in an attenuation of response, that is, habituation. Withdrawal responses elicited by anterior touch are controlled by anterior mechanosensory neurons (AVM and ALMs), and by four pairs of interneurons (AVA, AVB, AVD, and PVC) (Chalfie et al., 1985; White et al., 1986). To identify the neurons that participate in habituation, we ablated these neurons with a laser microbeam and investigated the resulting habituation of the operated animals. The animals lacking both left and right homologues AVDLR were habituated more rapidly than intact animals. We propose that chemical synapses at AVD play a critical role in the habituation of intact animals. 相似文献