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.
Margaret：细胞研究和治疗的监管标准
Margaret教授就细胞研究和治疗的监管标准将何去何从发表了演讲。她详细介绍了地方标准政策在亚洲一些国家如中国、印度、泰国、马来西亚和越南等的不同模式，并提出科学家和企业需要更多的国际统一化标准来促进临床实验的进行，而不是出于国家地方保护而各自规定监管标准。
Interplays between Mesenchymal Stem Cells and Immune Responses
Mesenchymal stem cells (MSCs) exist in almost all tissues and are crucial in maintaining the cellular homeostasis of multicellular organisms. They provide the ultimate cell source for tissue repair and regeneration. Under pathological conditions, these cells are awakened, activated, and mobilized to damaged tissue sites. Since tissue damages are often accompanied by inflammatory factors, from both innate immune response and adaptive immune response, it is sensible that MSCs delicately interact with inflammatory factors at the sites of tissue damages.
Depending on the type and persistence of the inflammatory factors, the activated MSCs could lead either to complete or partial tissue repair, or to chronic inflammation and further tissue damage, such as cancer and fibrosis. Indeed, recent studies have shown that there is a bidirectional interaction between MSCs and inflammatory cells and cytokines. However, much information of this information remains to be elucidated. Further investigations in this newly emerging exciting research area will undoubtedly lead to better understanding of pathogenesis of various diseases and novel treatment strategies.
Targets-based therapy for leukemia: opportunity and challenge
优点主要为：能增强患者的免疫力，防止肿瘤的转移和复发，对病人机体的损伤小。 在我国，现在普遍开展的树突状细胞（DC）和细胞因子诱导的杀伤细胞（CIK）的生物疗法被广泛应用。
Karen Dell: iBiology:Meet the world's best biologists through the Internet
Karen Dell来自美国细胞生物学学会，她将简述通过iBiology来获取生物学学习和交流的资源。
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.
Erich Gnaiger：Life Style and Mitochondrial Competence – Modern Drugs for T2 Diabetes in Aging and Degenerative Diseases.
D. Swarovski Research Laboratory (Mitochondrial Physiology), Dept. General, Visceral and Transplant Surgery, Innsbruck Medical University; and OROBOROS INSTRUMENTS, Innsbruck, Austria. - Email: erich.gnaiger@oroboros.at
The contribution of mitochondrial dysfunction to the etiology of T2 diabetes and a range of preventable metabolic diseases is the subject of intensive current research with world-wide health implications.
Recently these investigations gained depth and scope by technological advances for diagnosis of mitochondrial function by comprehensive OXPHOS analysis using high-resolution respirometry [1,2]. Fundamental questions of a causal relationship, however, between compromised mitochondrial function and development of T2 diabetes remain to be resolved [3,4] to optimize prevention and treatment of insulin resistance.
For preventable diseases such as T2 diabetes, the evolutionary background of mitochondrial competence provides a solid basis for improved and broad application of a well established modern drug, mtLSD.
Post-industrial societies are characterized by a high-energy input lifestyle with diminished physical activity and high incidence of non-transmittable diseases, in comparison to human populations where physical work is essentially important for sustaining life and in which degenerative diseases (T2 diabetes, various cancers, Alzheimer's) are essentially absent [5]. The capacity of oxidative phosphorylation (OXPHOS) is increased or maintained high by a life style involving endurance exercise and strength training [6].
Life style changes from the age of 20-30 years to the elderly, but is subject to change and intervention. Depending on group selection in cross-sectional studies, OXPHOS capacity declines from the age of 20-30 years [7,8], or is independent of age up to 80 years [9,10].
Independent of age, there is a strong decline of OXPHOS capacity in human vastus lateralis from BMI of 20 to 30 [1]. At a BMI >30, a threshold OXPHOS capacity is reached in human v. lateralis that may be characteristic of a low-grade inflammatory state (‘mitochondrial fever’).
Onset of degenerative diseases (T2 diabetes, neuromuscular degeneration, various cancers) and mitochondrial dysfunction interact in an amplification loop progressing slowly with age, such that cause and effect of mitochondrial dysfunction cannot be distinguished. Diminished antioxidant capacity at low mitochondrial density is an important mechanistic candidate in the state of mitochondrial fever.
For implementing a life style supporting mitochondrial competence and preventing degenerative diseases in modern societies, we need (1) extended research programmes focused on the causative link between mitochondrial competence and effective prevention of degenerative diseases, (2) educational programmes on mitochondrial physiology targeted at general practitioners, teachers and the society at large, (3) cooperation of health care and insurance organizations to support preventive life style activities, and (4) do not miss any opportunity in taking the lead in living the mtLife Style Drug (mtLSD).
Affymetix芯片原理--陈巍学基因（28）
陈巍学基因这个节目，主要是为大家介绍基因组学，和临床分子诊断的最新技术进展.
今天，主要和大家谈一下著名的生物芯片公司 Affymetrix 公司，以及它应用得最广的两种芯片：表达谱芯片、和SNP分型芯片。主要分为以下几个部分：
1.Affymetrix 芯片的制造过程，类似半导体芯片的制造过程，是通过光蚀刻来完成的。
2.Affymetrix 的表达谱芯片，分成传统的In Vitro Transcription 芯片和Whole Transcriptome 芯片。
3.Affymetrix 公司的基因分型芯片，也就是SNP分型芯片有两种实验原理：新的是Axiom芯片，是基于连接反应的；而老的卡式芯片，是基于目标DNA片段与探针序列进行杂交。
4.Affymetrix 分析表达谱的软件。
端粒和端粒酶的作用 - Elizabeth Blackburn P1
本视频由科普中国和生物医学大讲堂出品
Elizabeth Blackburn (UCSF) Part 1: The Roles of Telomeres and Telomerase
Lecture Overview
Telomerase, a specialized ribonucleprotein reverse transcriptase, is important for long-term eukaryotic cell proliferation and genomic stability, because it replenishes the DNA at telomeres. Thus depending on cell type telomerase partially or completely (depending on cell type) counteracts the progressive shortening of telomeres that otherwise occurs. Telomerase is highly active in many human malignancies, and a potential target for anti-cancer approaches. Furthermore, recent collaborative studies have shown the relationship between accelerated telomere shortening and life stress and that low telomerase levels are associated with six prominent risk factors for cardiovascular disease.