sRNA Induces the Large-scale Transdetermination of Mesenchymal Stem Cells into Hematopoietic Stem Cells in Human.
Mesenchymal stem cells (MSCs) can differentiate into cells of bone, endothelium, adipose tissue, cartilage, muscle, and brain. However, whether they can transdeterminate into hematopoietic stem cells (HSCs) remains unsolved. We report here that a subpopulation of human MSCs that are CD44+,CD29+, CD105+, CD166+,CD133-,CD34- could differentiate into hematopoietic stem cells (CD150+/CD133+/CD34+) and their descending blood cells in vitro, when transfected with new endogenous shRNAs The sRNA was high-effectively delivered into MSCs by a novel peptide means. These induced MSC-HSCs could form different types of hematopoietic colonies as nature-occurring HSCs did. Upon transplantation into sublethally irradiated NOD/SCID mice, these MSC-HSCs engrafted and differentiated into all hematopoietic lineages such as erythrocytes, lymphocytes, myelocytes and thrombocyte. More importantly, these induced HSCs could successfully engraft and effectively function in patients with severe aplastic anemia. Furthermore, we demonstrated the first evidence that the transdetermination of MSCs was induced by acetylation of histone proteins and activation of many transcriptional factors. Together, our findings identify the sRNAs that dictates a directed differentiation of MSCs toward HSCs and open up a new source for HSCs used for the treatment of blood diseases and artificial stem cell-made blood.
immunotherapy against cancers(position of sellular therapy)
Discovery: Innovations with Ed Begley Jr
美国著名的《Discovery》频道创新系列节目《Innovations with Ed Begley Jr》全球播出了艾森生物最新研发的新一代实时心肌功能评价系统(xCELLigence RTCA CardioECR)。
本期节目主要关注在医疗健康领域的突破性进展。节目用七分多钟时间报道了艾森生物实时心肌细胞检测这项突破性的技术发明,并通过目前用药安全方面的问题调研及业内知名专家的采访,阐明了该发明在药物早期心脏毒性评价、用药安全、高通量新药筛选、心脏基础研究方面的价值和意义。
Simultaneous quantification of 47 gene expression in FFPE samples by a novel PCR-free approach
基因表达(gene expression)是指细胞在生命过程中,把储存在DNA顺序中遗传信息经过转录和翻译,转变成具有生物活性的蛋白质分子。生物体内的各种功能蛋白质和酶都是同相应的结构基因编码的。差别基因表达(differential gene expression)指细胞分化过程中,奢侈基因按一定顺序表达,表达的基因数约占基因总数的5%~10%。
ion Torrent测序 - 陈巍学基因(13)
ionTorrent是最新一代的测序技术,它的核心技术是使用半导体技术在化学和数字信息之间建立直接的联系。在半导体芯片的微孔中的微球上固定DNA链,随后依次掺入ACGT。随着每个碱基的掺入,释放出氢离子,在它们穿过每个孔底部时能被检测到,通过对H+ 的检测,实时判读碱基。
於莉:新一代ion半导体测序技术在医学检测与研究中的应用
演讲主要内容:
测序技术的发展
测序的原理
高通量测序仪
基因测序与人类健康
基因测序在临床医学的应用
ion测序平台介绍
NGS与转化医学
靶向测序解决方案等
陈琦:新一代ion 半导体测序技术在医学检测与研究中的应用
本次讲座重点介绍ion 测序技术在临床医学检测与研究中的应用,包括肿瘤个性化 治疗、疾病基因风险预估、无创产前筛查、新生儿遗传病筛查等领域的进展与前景。
李于:SIRT1 Regulation of Energy Metabolism: Attenuation of Hepatic Steatosis and Obesity
Fibroblast growth factor 21 (FGF21) is the hepatocyte-derived hormone that regulates fatty acid metabolism and has potential to treat obesity and diabetes. We recently indicate that hepatic overexpression of SIRT1 in diabetic mice attenuates hepatic steatosis and insulin resistance. However, the in vivo long-term consequence of hepatic SIRT1 ablation in liver physiology remains unknown.
We showed that hepatocyte-specific SIRT1 knockout (SIRT1 LKO) mice with the albumin Cre-loxP system exhibited a striking phenotype with greater propensity for obesity on a chow diet, characterized by increased whole body mass and fat mass, reduced energy expenditure, and unaltered food intake and physical activity. The obese phenotypes of SIRT1 LKO mice were associated with reduced hepatic and circulating levels of fasting FGF21.
Hepatic impairment of FGF21 repressed expression of key enzymes involving fatty acid oxidation such as CPT1α and MCAD, and inhibited expression of ketogenic enzymes including ACAT1, HMGCS2, HMGCL, and BDH1, thereby reducing plasma β–hydroxybutyrate levels in SIRT1 LKO mice. Moreover, transcriptional activity of a FGF21 promoter-driven luciferase reporter was stimulated by SIRT1 activators, resveratrol and SRT1720, in SIRT1+/+ MEFs, but not in SIRT1-/- MEFs.
The ability of resveratrol and SRT1720 to stimulate FGF21 protein was abolished by SIRT1 H335A inactive mutant or by nicotinamide and splitomicin in HepG2 cells. Induction of FGF21 by SIRT1 activators enhanced expression of key enzymes for fatty acid oxidation and ketogenesis.
These in vivo and in vitro findings characterize 1) hepatic SIRT1 as a master regulator of FGF21; 2) SIRT1-dependent activation of FGF21 in liver as a component for adaptive fasting response; and 3) defective hepatic SIRT1 and FGF21 signaling as a key pathological determinant of energy metabolic abnormality and obesity susceptibility.
金颖:Fox3 suppresses NFAT-mediated differentiation to maintain self-renewal of embryonic stem cells
金颖教授为分子发育生物学研究室主任,健康科学中心研究员。金教授介绍了Fox3通过抑制NFAT介导的分化维持了胚胎干细胞的自我更新的机制等前沿发现。
Pluripotency-associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, molecular mechanisms underlying its function are largely unknown.
Here, we report that Foxd3 suppresses differentiation induced by Calcineurin-NFAT signaling to maintain the ESC identity. Mechanistically, Foxd3 interacts with NFAT proteins and recruits co-repressor Tle4, a member of the Tle suppressor family highly expressed in undifferentiated ESCs, to repress NFATc3’s transcriptional activities.
Furthermore, global transcriptome analysis shows that Foxd3 and NFATc3 co-regulate a set of differentiation-associated genes in ESCs. Collectively, our study establishes a molecular and functional link between a pluripotency-associated factor and an important ESC differentiation-inducing pathway.
贾立军:Neddylation蛋白修饰-CRL 泛素连接酶通路调控肿瘤细胞自噬应答的机制与潜在应用
贾立军博士,复旦大学附属肿瘤医院肿瘤研究所研究员和博士生导师。目前主要从事“针对蛋白质翻译后修饰通路进行抗肿瘤分子靶点发现”等研究工作。
相关研究在 J Natl Cancer Inst(JNCI)、Cancer Research、Clinical Cancer Research、Autophagy、Cell Death & Differentiation、Cell Death & Disease、Int J Cancer和J Biol Chem等学术期刊发表文章40篇、获邀参编英文专著4部。主持国家自然科学基金(81372196,31071204,30500637,81172092)、国家重大科学研究计划(2012CB910302,课题负责)、上海市卫生局A类重点项目 (2010012)、上海市“浦江人才 ”资助计划(12PJ1400600)和上海高校特聘教授(东方学者)资助计划等科研项目。
学术兼职包括:国家自然科学基金委员会医学科学领域学科评审组专家、中华医学科技奖评审委员会委员、上海市免疫学会肿瘤免疫专业委员会委员、高等学校自然科学奖和技术发明奖评审专家和十余种学术期刊审稿专家。荣获上海高校特聘教授(东方学者)和上海市浦江人才等荣誉称号。