SMall RNA-seq - 陈巍学基因（9）
本期课程介绍：
1、SMall RNA建库测序的方法；
2、SMall RNA测序数据的生物信息学分析（A、表达量差异分析；B、聚类分析；C、GO分析；D、KEGG Pathway分析）；
3、血清和血浆micro RNA测序的意义、和样本准备
Duolink实验——利用PLA技术检测SMad复合体
BMP4_SMad信号通路具有非常重要的作用，研究表明BMP4通过SMad1/5/8信号通路可促进哺乳动物卵原干细胞分化。该课程详细讲述了通过原位PLA技术可检测到BMP4信号转导下游效应因子SMad1/5/8与SMad4形成复合体，进而激活一系列基因的转导。
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.
CytoplaSM是什么？
Margaret Gardel探讨细胞质的物理性质，一个复杂的流体内的细胞，是挤满了蛋白质，细胞器和丝状网络。她沉思，例如，运动蛋白如何克服身体携带的货物的阻力，以及如何细胞进行形状的变化，以应对不同的刺激。为了帮助解决这些问题，她提出了一个“新物理学”。
质谱代谢组学技术：精准医学的赋能者—Beyond biomarker, towards mechaniSM
众所周知，多组学（Multi-Omics）技术是精准医学研究的重要抓手之一，不同组学研究能为揭示疾病标志物与致病机制提供不同分子层次上的有益视角。有容乃大，众行则远，针对不同疾病的特性与研究需求，灵活调配各种组学技术，兼容并用，已然成为精准医学实践中自觉自发的一种研究模式，引人关注，蔚为大观。作为生物信息流传递的下游与遗传-暴露因素复杂互作级联效应的读取器，生物体液中富蕴的代谢组信息与生物表型之间存在着天然上的最大似然，代谢组学技术在既往的转化医学研究中呈现出的价值人所共知。正如学界倡议的那样直截了当，Metabolomics Enables Precision Medicine！此次，让我们一起回顾代谢组学与转化医学守望相助、风云激荡的过往，纵观技术的悄然进步如何成就精准医学更好的现下与将来。主要分享的内容有： • 以史为鉴，继往开来：代谢组学在精准医学中的应用与启示 • 盘马弯弓，引而待发：质谱代谢组学的技术体系与研究流程 • 西北望，射天狼：最新技术进展之从非靶向到靶向、从谱库到云端的全面出击 • 结语：了却客户烦心事
A study on mechaniSM and function of androgen-responsive non-coding RNAs in Prostate Cancer
近年来大量研究表明非编码RNA在人类疾病的调控中扮演了越来越重要的角色。包括肿瘤、神经系统疾病、心血管病的发生、以及参与免疫与代谢疾病调控、精子发育调控等，为开发疾病诊断标志物以及筛选新药靶标带来诸多新的方向。本次网络研讨会将围绕非编码RNA调控机理， 技术方法以及与疾病关系邀请名专家学者座谈，分享最新非编码RNA研究成果与经验，推动学科发展，促进转化医学及合作。