共查询到20条相似文献，搜索用时 0 毫秒
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Sofie De Schepper Joachim Boucneau Jo Lambert Ludwine Messiaen Jean‐Marie Naeyaert 《Pigment cell & melanoma research》2005,18(1):13-24
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, affecting approximately 1 in 3500 individuals. The most commonly seen tumors in NF1 patients are the (sub)cutaneous neurofibromas. However, individuals with NF1 typically present in childhood with well‐defined pigmentary defects, including café‐au‐lait macules (CALMs), intertriginous freckling and iris Lisch nodules. NF1 is considered a neurocristopathy, primarily affecting tissues derived from the neural crest. Since the pigment producing melanocyte originates in the neural crest, the presence of (hyper)pigmentary lesions in the NF1 phenotype because of changes in melanocyte cell growth and differentiation is to be expected. We want to discuss the pigmentary cutaneous manifestations of NF1 represented by CALMs and intertriginous freckles and the pigmentary non‐cutaneous manifestations represented by iris Lisch nodules. Several hypotheses have been suggested in explaining the poorly understood etiopathogenesis of CALMs. Whether other pigmentary manifestations might share similar etiopathogenic mechanisms remains obscure. Additional attention will be drawn to a readily seen phenomenon in NF1: hyperpigmentation overlying (plexiform) neurofibromas, which could suggest common etiopathogenetic‐environmental cues or mechanisms underlying CALMs and neurofibromas. Finally, we want to address the relationship between malignant melanoma and NF1. 相似文献
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Lena Feuerer Susanne Lamm Ingmar Henz Melanie Kappelmann‐Fenzl Sebastian Haferkamp Svenja Meierjohann Claus Hellerbrand Silke Kuphal Anja Katrin Bosserhoff 《Pigment cell & melanoma research》2019,32(6):777-791
The protein melanoma inhibitory activity (MIA) is known to be expressed in melanoma and to support melanoma progression. Interestingly, previous studies also observed the expression of MIA in nevi. Concentrating on these findings, we revealed that MIA expression is correlated with a senescent state in melanocytes. Induction of replicative or oncogene‐induced senescence resulted in increased MIA expression in vitro. Notably, MIA knockdown in senescent melanocytes reduced the percentage of senescence‐associated beta‐Gal‐positive cells and enhanced proliferation. Using the melanoma mouse model Tg(Grm1), MIA‐deficient mice supported the impact of MIA on senescence by showing a significantly earlier tumor onset compared to controls. In melanocytes, MIA knockdown led to a downregulation of the cell cycle inhibitor p21 in vitro and in vivo. In contrast, after induction of hTERT in human melanoma cells, p21 regulation by MIA was lost. In summary, our data show for the first time that MIA is a regulator of cellular senescence in human and murine melanocytes. 相似文献
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1型糖尿病（T1D）是一种慢性、多因素自身免疫性疾病,在发病过程中,会不断破坏胰岛β细胞,最终导致胰岛素分泌不足, 严重威胁人类健康。目前,根治T1D的主要方法是胰岛移植,即将移植的胰岛替代体内已被疾病破坏的胰岛细胞,以恢复正常血糖。但 是,胰岛移植供体的缺乏和移植免疫排斥反应,给胰岛移植的临床应用带来巨大挑战。近年来,干细胞治疗为T1D提供了一种新疗法, 成为T1D治疗领域新的研究热点,为该病的治疗提供了新思路。综述不同来源干细胞——胚胎干细胞、诱导多能干细胞和成体干细胞用 于治疗T1D的研究进展。 相似文献
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NF1 is a tumour suppressor gene, germline mutations of which lead to neurofibromatosis type 1 syndrome. Patients develop benign tumours from several types of cells including neural crest‐derived cells. NF1 somatic mutations also occur in 15% of sporadic melanoma, a cancer originating from melanocytes. Evidence now suggests the involvement of NF1 mutations in melanoma resistance to targeted therapies. Although NF1 is ubiquitously expressed, genetic links between NF1 and genes involved in melanocyte biology have been described, implying the lineage‐specific mechanisms. In this review, we summarize and discuss the latest advances related to the roles of NF1 in melanocyte biology and in cutaneous melanoma. 相似文献
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胚胎干细胞在再生医学领域有着十分诱人的应用前景。但是现有胚胎干细胞建系技术不能避开对卵细胞的操作, 成为ES细胞临床应用的障碍。通过反转录病毒载体系统, 在小鼠和人类高度分化细胞中表达干细胞因子Oct4, Sox2, Klf4和/或c-Myc等基因, 再经过干细胞标志因子Nanog或Oct4筛选, 可以获得与ES细胞特性十分近似的诱导多能干细胞系。这种不依赖于卵细胞的多能干细胞建系方法无疑是干细胞实验技术的重大进展, 也是对现有重编程理论假设的突破。综述了诱导多能干细胞系建系实验结果, 并对诱导重编程的机制和诱导多能干细胞系的临床应用前景进行了讨论。 相似文献
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Germana Falcone Alessia Mazzola Flavia Michelini Gianluca Bossi Federica Censi Maria G. Biferi Luisa Minghetti Giovanna Floridia Maurizio Federico Antonio Musio Marco Crescenzi 《Aging cell》2013,12(2):312-315
Senescence is thought to be triggered by DNA damage, usually indirectly assessed as activation of the DNA damage response (DDR), but direct surveys of genetic damage are lacking. Here, we mitotically reactivate senescent human fibroblasts to evaluate their cytogenetic damage. We show that replicative senescence is generally characterized by telomeric fusions. However, both telomeric and extratelomeric aberrations are prevented by hTERT, indicating that even non‐telomeric damage descends from the lack of telomerase. Compared with replicative senescent cells, oncogene‐induced senescent fibroblasts display significantly higher levels of DNA damage, depicting how oncogene activation can catalyze the generation of further, potentially tumorigenic, genetic damage. 相似文献
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Xiaoling Guo Xiaohong Gu Sohun Hareshwaree Xing Rong Lei Li Maoping Chu 《Journal of cellular and molecular medicine》2019,23(6):4358-4374
Induced pluripotent stem cell‐derived conditioned medium (iPS‐CM) could improve cell viability in many types of cells and may be a better alternative for the treatment of myocardial infarction. This study aimed to examine the influence of iPS‐CM on anti‐apoptosis and the proliferation of H9C2 cardiomyocytes and investigate the underlying mechanisms. H9C2 cardiomyocytes were exposed to 200 μmol/L hydrogen peroxide (H2O2) for 24 hours with or without pre‐treatment with iPS‐CM. The ratio of apoptotic cells, the loss of mitochondrial membrane potential (△Ψm) and the levels of intracellular reactive oxygen species were analysed by flow cytometric analysis. The expression levels of BCL‐2 and BAX proteins were analysed by Western blot. Cell proliferation was assessed using cell cycle and EdU staining assays. To study cell senescence, senescence‐associated β‐galactosidase (SA‐β‐gal) staining was conducted. The levels of malondialdehyde, superoxide dismutase and glutathione were also quantified using commercially available enzymatic kits. The results showed that iPS‐CM containing basic fibroblast growth factor significantly reduced H2O2‐induced H9C2 cardiomyocyte apoptosis by activating the autophagy flux pathway, promoted cardiomyocyte proliferation by up‐regulating the Wnt/β‐catenin pathway and inhibited oxidative stress and cell senescence. In conclusion, iPS‐CM effectively enhanced the cell viability of H9C2 cardiomyocytes and could potentially be used to inhibit cardiomyocytes apoptosis to treat myocardial infarction in the future. 相似文献
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Won-Young Choi Ji-Hyun Hwang Ann-Na Cho Andrew J. Lee Inkyung Jung Seung-Woo Cho Lark Kyun Kim Young-Joon Kim 《Molecules and cells》2020,43(12):1011
Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation. 相似文献
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