Nuclear reprogramming by nuclear transplantation and defined transcription factors

In the past ten years, great breakthroughs have been achieved in the nuclear reprogramming area. It has been demonstrated that highly differentiated somatic cell genome could be reprogrammed to a pluripotent state, which indicates that differentiated cell fate is not irreversible. Nuclear transplantation and induced pluripotent stem (iPS) cell generation are the two major approaches to inducing reprogramming of differentiated somatic cell genome. In the present review, we will summarize the recent progress of nuclear reprogramming and further discuss the potential to generate patient specific pluripotent stem cells from differentiated somatic cells for therapeutic purpose. Supported by the National High Technology Research and Development Program of China (Grant No. 2005AA210930)     

Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor

Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.     

拟南芥bHLH家族转录因子DYT1在花药发育过程中调控胼胝质降解(英文)

胼胝质的合成和降解是雄配子体减数分裂过程中的一个重要特征,对后期花粉成熟有重要作用.在此研究中,分离到了一个雄性不育突变体msl57,该突变体的绒毡层分化及胼胝质降解过程出现异常,导致花粉败育.图位克隆和遗传分析表明:MSl57基因与bHLI-I家族转录因子DYTI(At4g21330)是同一基因.因此,将ms157突变体改名为dyt1-2.反式激活作用实验揭示了DYTI的激活功能域位于基因的250 ～504bp之间.通过酵母双杂交实验发现DYT1蛋白在体内可以形成同源二聚体来执行其功能.RT-PCR及定量PCR分析表明胼胝质酶相关基因A6的表达在突变体背景下严重下调.因此,DVF1通过调控胼胝质的降解来影响花药发育过程.     

Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1.

Cohesion between sister chromatids is established during DNA replication and depends on a multiprotein complex called cohesin. Attachment of sister kinetochores to the mitotic spindle during mitosis generates forces that would immediately split sister chromatids were it not opposed by cohesion. Cohesion is essential for the alignment of chromosomes in metaphase but must be abolished for sister separation to start during anaphase. In the budding yeast Saccharomyces cerevisiae, loss of sister-chromatid cohesion depends on a separating protein (separin) called Esp1 and is accompanied by dissociation from the chromosomes of the cohesion subunit Scc1. Here we show that Esp1 causes the dissociation of Scc1 from chromosomes by stimulating its cleavage by proteolysis. A mutant Scc1 is described that is resistant to Esp1-dependent cleavage and which blocks both sister-chromatid separation and the dissociation of Scc1 from chromosomes. The evolutionary conservation of separins indicates that the proteolytic cleavage of cohesion proteins might be a general mechanism for triggering anaphase.     

转录因子Bach1在心血管疾病中的研究进展

转录因子Bach1(BTB-CNC同源体1, BTB and CNC homology 1)是一种转录抑制因子, 广泛存在于哺乳动物的各种组织中. Bach1能抑制血红素环氧化酶-1(heme oxygenase-1, HO-1)等抗氧化基因的表达, 参与氧化应激反应. Bach1基因敲除对心肌缺血再灌注损伤有保护作用. 近期研究发现Bach1能抑制Wnt/b-catenin信号通路和小鼠缺血下肢血管新生. 主要就Bach1在心血管疾病中的研究进展进行简要综述.