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.
Eric TOPol:未来医疗的无线化
EricTOPol说，我们很快就可以通过智能手机来监控我们的生命体征并监测一些慢性疾病。在TEDMED上，他着重介绍了应用在未来医疗上的一些重要无线装置，这些装置可以帮助我们远离医院的病床。
ChrisTOPher deCharms:即时扫描大脑的技术
神经科学家和发明家ChrisTOPher deCharms展示一种新的方式利用功能磁共振成像显示大脑活动-思想，情感，痛苦-当它正在发生时。换句话说，你可以看到你的感受。
秦正红：DRAM1 regulates auTOPhagy flux and Bid-mediated cell death via lysosomes
秦正红，博士，教授，神经药理专业博士生导师。1994年在美国宾州医学院研究生院获博士学位，先后在美国国家卫生研究院(NIH)及麻省总医院和哈佛大学医学院从事研究工作。2003年从哈佛大学引进，现为苏州大学医学部基础医学与生物科学学院科研中心实验室主任，中国药理学会生化药理学专业委员会委员，中国药理学会神经药理学专业委员会委员，美国神经科学学会会员。
Damage-regulated auTOPhagy modulator1 (DRAM1), a novel TP53 target gene, is an evolutionarily conserved lysosomal protein and plays an essential role in TP53-dependent auTOPhagy activation and apoptosis (Crighton et al, 2006). However, the mechanisms by which DRAM1 promotes auTOPhagy and apoptosis are not clear.
3-Nitropropionic acid (3-NP) is an inhibitor of mitochondrial respiratory complex II. Intrastriatal administration of 3-NP produces neuropathology resemble to Huntington disease. 3-NP-induced neuronal death was involved in auTOPhagy and apoptosis. In vitro studies with 3-NP in TP53 wt and null cells, 3-NP or CCCP increased the protein levels of DRAM1 in a TP53-dependent or independent manner. DRAM1 induction contributed to 3-NP-induced auTOPhagy activation. Knock-down of DRAM1 with siRNA inhibited the activity of V-ATPase, acidification of lysosomes and activation of lysosomal proteases. Knock-down of DRAM1 reduced the clearance of auTOPhagososmes.
3-NP also induced a transcription independent upregulation of BAX protein levels. Knock-down of DRAM1 suppressed the increase in BAX levels. Co-immunoprecipitation and pull-down studies revealed an interaction of DRAM1 and BAX protein. Stably expression of exogenous DRAM1 increased the half-life of BAX. Upregulation of DRAM1 recruited BAX to lysosomes and induced cathepsin B-dependent cleavage of Bid and cytochrome c release. Knockdown of DRAM1, BAX or inhibition of lysosomal enzymes reduced 3-NP-induced cytochrome c release and cell death.
These data suggest that DRAM1 plays important roles in regulating auTOPhagy flux and apoptosis. DRAM1 promotes auTOPhagy flux through a mechanism involves activation of V-ATPase and enhances the acidification of lysosomes. DRAM1 promotes apoptosis via a mechanism involving recruitment of BAX to lysosomes to trigger cathepsin B-mediated Bid cleavage.
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”。