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【bio-news】2009年1月干细胞研究领域最新进展
Vol. 323. no. 5911, pp. 248 - 251
DOI: 10.1126/science.1165678
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Reports
Drosophila Stem Cells Share a Common Requirement for the Histone H2B Ubiquitin Protease Scrawny
Michael Buszczak,* Shelley Paterno, Allan C. Spradling
Stem cells within diverse tissues share the need for a chromatin configuration that promotes self-renewal, yet few chromatin proteins are known to regulate multiple types of stem cells. We describe a Drosophila gene, scrawny (scny), encoding a ubiquitin-specific protease, which is required in germline, epithelial, and intestinal stem cells. Like its yeast relative UBP10, Scrawny deubiquitylates histone H2B and functions in gene silencing. Consistent with previous studies of this conserved pathway of chromatin regulation, scny mutant cells have elevated levels of ubiquitinylated H2B and trimethylated H3K4. Our findings suggest that inhibiting H2B ubiquitylation through scny represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes
http://www.sciencemag.org/cgi/content/abstract/1165678
干细胞具有无与伦比的多能性，它可以转变为任意一种细胞类型，因此干细胞是科研者的心头好，因为，对再生医学领域来说这是多么有意义的治疗手段。
现在，卡内基研究所的一队研究小组鉴定了一个维持干细胞多能性的关键基因，他们将这个基因命名为scrawny，研究结果发现在干细胞未分化期间，这个基因对保持干细胞的多能性具有关键的意义。研究小组认为，了解干细胞多能性的维持机制不仅对细胞生物学研究来说很重要，还对医学应用研究也十分有意义。
卡内基研究所胚胎学系的主任Allan C.Spradling说，每个生物体的组织器官的功能都依仗干细胞的多能性而得以维持。然而，到目前为止，科学家们还不了解干细胞的多能性是如何得以维持的。
在这项研究中，Spradling和同事Michael Buszczak，Shelley Paterno以果蝇为研究对象，鉴定了一个新基因，命名为scrawny，该基因编译的蛋白具有修饰特殊染色体蛋白H2B的能力，H2B主要功能是包装DNA，使其成为染色体。研究者发现scrawny能修饰蛋白沉默基因表达借以控制干细胞的定向分化过程，比如说，控制干细胞分化成皮肤细胞或是肠细胞。
研究小组观察了果蝇的每种细胞类型的分化过程中scrawny的控制作用，如果scrawny发生突变，果蝇将失去组织修复再生的能力，具体来说，当皮肤受到损伤后干细胞生成新的皮肤细胞。
Spradling说，干细胞是维持机体修复功能的主要细胞，失去多能性的干细胞将无法修复组织。尽管现阶段的研究是在果蝇体内开展的，我们相信多细胞动物体内也有相似的基因存在，包括人类。这一研究成果是干细胞研究中的一个重大发现。对scrawny的了解有助人们加深对干细胞的了解，也为研究干细胞定向分化提供了新的途径.
Letters to Nature p.200
http://www.nature.com/nature/journal/v457/n7226/abs/nature07475.html
Nature 457, 200-204 (8 January 2009) | doi:10.1038/nature07475; Received 7 April 2008; Accepted 26 September 2008; Published online 19 November 2008
Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours
Sandra Rebouissou1,2, Mohamed Amessou1,2, Gabrielle Couchy1,2, Karine Poussin1,2, Sandrine Imbeaud3,4, Camilla Pilati1,2, Tina Izard5, Charles Balabaud6,7, Paulette Bioulac-Sage6,8 & Jessica Zucman-Rossi1,2
Inserm, U674, Génomique fonctionnelle des tumeurs solides, Paris F-75010, France
Université Paris Diderot, Paris 7, Institut Universitaire d'Hématologie, Paris F-75010, France
Array s/IMAGE, Genexpress, Functional Genomics and Systems Biology for Health, UMR 7091 CNRS; Université Paris 6 Pierre et Marie Curie, Villejuif F-94801, France
Gif/Orsay DNA Microarray Platform (GODMAP), Centre de Génétique Moléculaire, UPR 2167 CNRS; Université Paris-Sud 11, Gif-sur-Yvette F-91198, France
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA
Inserm, U889; Université Victor Segalen Bordeaux 2, IFR66, Bordeaux F-33076, France
CHU de Bordeaux, Hôpital Saint-André, Service d'hépatologie, Bordeaux F-33076, France
CHU de Bordeaux, Hôpital Pellegrin, Service d'Anatomie Pathologique, Bordeaux F-33076, France
Correspondence to: Jessica Zucman-Rossi1,2 Correspondence and requests for materials should be addressed to J.Z.-R. (Email: zucman@cephb.fr).
Top of pageInflammatory hepatocellular adenomas are benign liver tumours defined by the presence of inflammatory infiltrates and by the increased expression of inflammatory proteins in tumour hepatocytes1, 2. Here we show a marked activation of the interleukin (IL)-6 signalling pathway in this tumour type; sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene, which encodes the signalling co-receptor gp130. Indeed, 60% of inflammatory hepatocellular adenomas harbour small in-frame deletions that target the binding site of gp130 for IL-6, and expression of four different gp130 mutants in hepatocellular cells activates signal transducer and activator of transcription 3 (STAT3) in the absence of ligand. Furthermore, analysis of hepatocellular carcinomas revealed that rare gp130 alterations are always accompanied by -catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas fully explains activation of the acute inflammatory phase observed in tumourous hepatocytes, and suggests that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.
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作者:admin@医学,生命科学 2011-08-13 05:11
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