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1.
干细胞中两个关键细胞因子Oct4和Sox2   总被引:1,自引:0,他引:1  
胚胎干细胞(ESC)在谱系特异性标志被激活前,Oct4和Sox2蛋白水平是细胞向谱系选择发展过程中的连续临时性标志。Oct4和Sox2转录因子在启动细胞重编程、维持ESC多能性和决定其是否走向分化方面具有关键作用。它通过与靶基因调控区结合,选择性地抑制分化基因或者激活多能性基因的表达而达到调控目的。干细胞共激活复合物(SCC)是Oct4和Sox2在Nanog基因协同激活时所需要的,它直接与Oct4和Sox2相互作用并集中在Nanog和Oct4启动子部位以及大部分被Oct4和Sox2占据的基因组区域,在维持ES细胞多能性和保持基因组完整性方面发挥着重要功能。因此,对Oct4、Sox2这两个关键性细胞因子作用机制深入了解,有助于细胞重编程分子机制的进一步阐明,为干细胞的相关研究奠定基础。  相似文献   

2.
雌性多能干细胞(iPS细胞)多能性状态的获得伴随着X染色体的表观修饰重编程。分化终末状态的雌性体细胞中有1条X染色体发生异染色质化而导致其失活。在体细胞诱导多能性干细胞的过程中,失活的X染色体重新活化。在重编程过程中,多能因子和X染色体失活中心的非编码基因的联系紧密。文章主要从分子水平上讨论多能干细胞X染色体表观修饰的相关研究进展。小鼠胚胎干细胞(ES细胞)是标准的多能性基态。X染色体上非编码RNA的表达可能是一个评价iP S表观遗传状态的标记,相关研究可以为细胞治疗的临床应用提供重要依据。  相似文献   

3.
POU(Pit-Oct-Unc)域转录因子Oct-3/4已成为小鼠、人、猕猴等哺乳动物体内多能性胚胎干细胞的标志物。在小鼠胚胎发育过程中,Oct-3/4基因只在全能和多能细胞中表达。研究Oct-3/4表达部位及作用机制已成为研究胚胎形成过程及细胞分化过程的必要手段。本文综述了Oct-3/4的表达特性及人、牛、猪、小鼠之间Oct-3/4的结构差异,并详细的描述了其作用机制。  相似文献   

4.
POU(Pit-Oct-Unc)域转录因子Oct-3/4已成为小鼠、人、猕猴等哺乳动物体内多能性胚胎干细胞的标志物。在小鼠胚胎发育过程中,Oct-3/4基因只在全能和多能细胞中表达。研究Oct-3/4表达部位及作用机制已成为研究胚胎形成过程及细胞分化过程的必要手段。本文综述了Oct-3/4的表达特性及人、牛、猪、小鼠之间Oct-3/4的结构差异,并详细的描述了其作用机制。  相似文献   

5.
脂肪细胞分化是一个多能间充质干细胞(MSCs)逐渐向成熟脂肪细胞分化的复杂过程,该过程受很多转录因子、激素以及信号通路相关分子的严格调控。体内外的试验表明,microRNAs(miRNAs)也参与了脂肪细胞分化的调节,且可以靶向转录因子和信号通路中的关键分子发挥作用。丝裂原活化蛋白激酶(MAPK)信号通路是真核细胞将胞外信号转导至胞内引起细胞反应的一类重要信号系统,研究证明,miRNAs可以靶向MAPK信号通路中的某些基因,影响该通路的信号转导,参与脂肪细胞分化的调控。因此本文总结了近几年有关miRNA改变MAPK信号转导,实现调控脂肪细胞分化功能的研究,以期为深入了解脂肪细胞分化的机制,为治疗脂肪型疾病提供新的思路。  相似文献   

6.
OCT4属于POU转录因子。目前对于OCT4基因的研究认为在鼠和人体内,OCT4主要表达于胚胎干细胞及生殖细胞中,对于维持胚胎干细胞的多能性和自我更新有十分重要的作用,对于胚胎早期发育具有重大意义。但是目前OCT4在小鼠早期胚胎中的结合位点还不清晰,应进一步深入研究OCT4基因构建OCT4在小鼠早期胚胎发育过程中的调控网络,为揭开胚胎早期发育调控机制的面纱提供重要参考。  相似文献   

7.
胰腺干细胞是一种多能干细胞,具有无限分裂和永久自我更新的能力,可在特定因素的影响或诱导下,分化成胰腺导管、胰岛、外分泌腺泡等特定胰腺组织类型,甚至肝细胞.由胰腺干细胞诱导分化的胰岛β细胞在治疗Ⅰ型糖尿病和纠正部分Ⅱ型糖尿病中具有重要意义.论文就胰腺干细胞的存在部位、诱导干细胞为胰岛β细胞的生物活性物质、诱导分化为胰腺β细胞的方法及调控胰腺干细胞分化的信号通路等方面做一综述.  相似文献   

8.
为研究鸡体细胞诱导重编程早期的糖代谢方式的变化,试验采用OCT4、SOX2、NANOG和LIN28A(OSNL)四因子诱导体系将鸡胚成纤维细胞(Chicken embryo fibroblasts,CEF)重编程为诱导多能干细胞(Induced pluripotent stem cells,iPS),并利用碱性磷酸酶染色、阶段特异性胚胎抗原1(Stage-specific embyronic antigen-1,SSEA-1)免疫荧光染色、体外诱导分化及多能性基因表达检测等对iPS进行鉴定。通过检测重编程过程中糖代谢相关基因表达及酶活性的变化,并对葡萄糖摄取量、乳酸产生量及线粒体膜电位检测等研究鸡体细胞诱导重编程早期的糖代谢变化。结果显示,鸡CEF诱导重编程形成的iPS呈碱性磷酸酶染色阳性,表达SSEA-1蛋白,体外分化形成类胚体且表达多能性标记基因。同时重编程过程中氧化磷酸化基因表达下调而糖酵解相关基因表达上调,糖酵解关键酶活性均增强,且iPS的葡萄糖吸收量及乳酸产生量增加,而线粒体膜电位则下降。结果表明,OSNL四因子体系将鸡CEF诱导重编程形成iPS的过程中,细胞的主要糖代谢方式从氧化磷酸化转变为糖酵解,而糖酵解的激活可能会进一步促进iPS的形成。  相似文献   

9.
胚胎干细胞是未分化的具有增殖和自我更新能力的细胞,并且能分化成所有类型的体细胞以及生殖细胞。它们提供了早期胚胎分化的体外模型,也是基因操作的重要靶细胞。禽类多能性干细胞培养最重要的应用领域是以干细胞体外遗传修饰、鉴定为技术平台的家禽转基因技术。通过此技术对禽类基因进行遗传修饰与操作,在胚胎发育基础研究、转基因禽类生产及家禽育种等方面有巨大的应用前景。但是禽类多能性干细胞培养的许多基本问题仍亟待解决,如探索其建系的培养条件、揭示其维持多能性和增殖能力的分子机制等。文章综述了禽类多能性干细胞的分离方法、体外分化能力、嵌合体形成以及基因修饰方面的研究进展及目前的研究局限。  相似文献   

10.
诱导多能干( induced pluripotent stem,iPS)细胞在维持多能的同时能够持续自我更新。由于诱导多能干细胞能够创造病人特异或者疾病特异的多能干细胞,这些细胞对于研究疾病的机理和药物的发现非常有用。作者主要从iPS细胞建立的优化、被重编程的细胞类型、iPS细胞的发育潜能、iPS细胞产生的2种模型及iPS细胞的应用等5个方面进行了综述。  相似文献   

11.
Nanog基因的生物学功能研究进展   总被引:1,自引:0,他引:1  
胚胎干细胞具有无限增殖能力和多向分化潜能决定了它在医学及生物学基础研究中具有巨大的应用潜力。探索维持胚胎干细胞特性的分子机制成为胚胎干细胞的生物学研究中的热点。研究发现与维持胚胎干细胞多能性相关的基因有Oct4、Nanog、Sox2等,其中Nanog是2003年5月末发现的一个基因,它对维持胚胎干细胞多能性起关键性作用,能够独立于L1F/Stats维持ICM和ES细胞的多能性。几年来,Nanog的生物学功能及其与Oct4、Sox2等多能性维持基因之间的相互作用关系已有较为深入的研究。作者在综述Nanog基因的表达特征和功能的基础上,重点探讨Nanog基因表达调控以及Oct4、Sox2等多能性维持基因之间的相互作用关系,并展望其应用前景。  相似文献   

12.
In the area of stem cell research, fusion of somatic cells into pluripotent cells such as mouse embryonic stem (ES) cells induces reprogramming of the somatic nucleus and can be used to study the effect of trans-acting factors from the pluripotent cell on the pluripotent state of somatic nucleus. As many other groups, we previously established a porcine pluripotent cell line at a low potential. Therefore, here, we performed experiments to investigate if the fusion with mouse ES cell could improve the pluripotent state of porcine pluripotent cell. Our data showed that resultant mouse–porcine interspecies fused cells are AP positive, and could be passaged up to 20 passages. Different degrees of increases in expression of porcine pluripotent genes proved that pig-origin gene network can be programmed by mouse ES. Further differentiation study also confirmed these fused cells’ potential to form three germ layers. However, unexpectedly, we found that chromosome loss and aberrant (especially in porcine chromosomes) is severe after the cell fusion, implying that interspecies cell fusion may be not suitable to study porcine pluripotency without additional supportive conditions for genome stabilization.  相似文献   

13.
14.
胚胎干细胞(embryonic stem cells,ES)是从早期囊胚内细胞团分离培养出来的能够不断维持自我更新和具有发育多能性的细胞。Wnt信号通路在维持胚胎干细胞的自我更新方面起着重要作用,糖原合成激酶 (glycogen synthase kinase-3,GSK-3)抑制剂可以激活Wnt信号通路,促进胚胎干细胞自我更新和增强细胞间连接。作者就GSK-3抑制剂在胚胎干细胞自我更新、细胞连接方面的作用及其作用机制进行简单综述。  相似文献   

15.
Small molecules discovered during the recent years can be used to regulate the growth of embryonic stem cells (ES cells). Chicken blastodermal cells (cBCs) play an important role in both basic and transgenic researches as an important ES cell. However, the regulatory mechanism of small molecules involved in the self‐renewal and pluripotency of cBCs remains unknown. This study revealed that the small molecule, SC1, can maintain cBCs in an undifferentiated, pluripotent state in serum‐ and feeder‐free E8 media without leukaemia inhibitory factor. Furthermore, SC1 inhibits downregulation of pluripotency‐related genes caused by retinoic acid and promotes the proliferation of cBCs. Furthermore, the results of this study indicated that SC1 functions by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation, thus promoting the expression of pluripotency‐related genes and maintaining the pluripotency of cBCs. The results also demonstrated that SC1 sustains the self‐renewal capacity and pluripotency of cBCs cells by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation. This kind of regulatory mechanism might be conserved in avian ES cells. Other molecules, similar to SC1, might provide insights into the molecular mechanisms that control the fate of stem cells and ultimately help in‐vivo stem cell biology and therapy.  相似文献   

16.
胚胎干细胞最重要的生物学特征是具有发育全能性。要想获得具有发育全能性的胚胎干细胞,必需选择适当胚龄的胚胎和用正确的分化抑制物。本文从鼠类胚胎干细胞的获得、维持及胚胎干细胞的特征、生物学功能以及其他哺乳动物胚胎干细胞的研究等方面综述了胚胎干细胞的最新研究进展。  相似文献   

17.
Diploid germ cells are thought to have pluripotency potential. We recently described a method to derive pluripotent stem cells (PSCs) from cultured spermatogonial stem cells (SSCs) by depleting Trp53 and Dmrt1, both of which are known suppressors of teratomas. In this study, we used this technique to analyze the effect of this protocol in deriving PSCs from the male germline at different developmental stages. We collected primordial germ cells (PGCs), gonocytes and spermatogonia, and the cells were transduced with lentiviruses expressing short hairpin RNA against Dmrt1 and/or Trp53. We found that PGCs are highly susceptible to reprogramming induction and that only Trp53 depletion was sufficient to induce pluripotency. In contrast, gonocytes and spermatogonia were resistant to reprogramming by double knockdown of Dmrt1 and Trp53. PSCs derived from PGCs contributed to chimeras produced by blastocyst injection, but some of the embryos showed placenta-only phenotypes suggestive of epigenetic abnormalities of PGC-derived PSCs. These results show that PGCs and gonocytes/spermatogonia have distinct reprogramming potential and also suggest that fresh and cultured SSCs do not necessarily have the same properties.  相似文献   

18.

Background

Production of chimeric mice is a useful tool for the elucidation of gene function. After successful isolation of embryonic stem (ES) cell lines, there are many methods for producing chimeras, including co-culture with the embryos, microinjection of the ES cells into pre-implantation embryos, and use of tetraploid embryos to generate the full ES-derived transgenic mice. Here, we aimed to generate the transgenic ES cell line, compare the production efficiency of chimeric mice and its proportion to yield the male chimeric mice by microinjected ES cells into 4- to 8-cell and blastocysts embryos with the application of Piezo-Micromanipulator (PMM), and trace the fate of the injected ES cells.

Results

We successfully generated a transgenic ES cell line and proved that this cell line still maintained pluripotency. Although we achieved a satisfactory chimeric mice rate, there was no significant difference in the production of chimeric mice using the two different methods, but the proportion of the male chimeric mice in the 4- to 8-cell group was higher than in the blastocyst group. We also found that there was no tendency for ES cells to aggregate into the inner cell mass using in vitro culture of the chimeric embryos, indicating that they aggregated randomly.

Conclusions

These results showed that the PMM method is a convenient way to generate chimeric mice and microinjection of ES cells into 4- to 8-cell embryos can increase the chance of yielding male chimeras compared to the blastocyst injection. These results provide useful data in transgenic research mediated by ES cells.  相似文献   

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