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Current progress and prospects of induced pluripotent stem cells. 诱导多能干细胞的研究进展与展望。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0092-6
LingYi Chen, Lin Liu

Induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of few transcription factors. Like embryonic stem (ES) cells, iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body. iPS cells hold great promise for regenerative medicine, because iPS cells circumvent not only immunological rejection but also ethical issues. Since the first report on the derivation of iPS cells in 2006, many laboratories all over the world started research on iPS cells and have made significant progress. This paper reviews recent progress in iPS cell research, including the methods to generate iPS cells, the molecular mechanism of reprogramming in the formation of iPS cells, and the potential applications of iPS cells in cell replacement therapy. Current problems that need to be addressed and the prospects for iPS research are also discussed.

诱导多能干细胞是通过少数转录因子的异位表达从体细胞中分化而来的。与胚胎干细胞(ES)细胞一样,iPS细胞能够无限地自我更新,并分化成体内所有类型的细胞。诱导多能干细胞在再生医学方面有着巨大的前景,因为诱导多能干细胞不仅可以避免免疫排斥,还可以避免伦理问题。自2006年首次报道iPS细胞的衍生以来,世界各地的许多实验室开始了对iPS细胞的研究,并取得了重大进展。本文综述了近年来诱导多能干细胞的研究进展,包括诱导多能干细胞的制备方法、诱导多能干细胞形成过程中重编程的分子机制以及诱导多能干细胞在细胞替代治疗中的潜在应用。讨论了目前需要解决的问题和iPS研究的前景。
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引用次数: 34
High level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDS. 脑组织中高水平的HIV-1 DNA浓度可将haart后艾滋病痴呆复合物或心血管疾病患者与艾滋病患者区分开来。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0085-5
Li Zhao, Derek C Galligan, Susanna L Lamers, Stephanie Yu, Lamia Shagrun, Marco Salemi, Michael S McGrath

Highly active antiretroviral treatment (HAART) has had a significant impact on survival of individuals with acquired immunodeficiency syndrome (AIDS); however, with the longer life-span of patients with AIDS, there is increasing prevalence of AIDS dementia complex (ADC) and other non-AIDS-defining illness, and cardiovascular diseases (CVD) are also common. The influence of these varied disease processes on HIV-1 DNA concentration in brain tissues has not been thoroughly assessed in the post-HAART era. The purpose of the current study is to clarify the impacts of ADC and other complications of HIV disease on the viral load in the brains in AIDS patients with post-HARRT. We examined autopsy specimens from the brains of thirteen patients who died from complications of AIDS with quantitative polymerase chain reaction (QPCR). All but one patient had received HAART prior to death since 1995. Two patients died with severe CVD, multiple cerebrovascular atherosclerosis (CVA) throughout the brain and five patients died with ADC. Six patients had no ADC/CVA. A QPCR was used to measure the presence of HIV-1 DNA in six brain tissues (meninges, frontal grey matter, frontal white matter, temporal subcortex, cerebellum and basal ganglia). In the post-HARRT era, for non-ADC/CVA patients, HIV-1 DNA concentration in brain tissues was statistically higher than that in patients with ADC. In a new finding, two patients who suffered from severe CVD, especially CVA, also had high concentrations of HIV-1 in brain compartments not showing ADC related changes. To our knowledge, this is the first report of a relationship between the CVA and HIV-1 viral burden in brain. The current observations suggest that HAART-resistant HIV reservoirs may survive within ADC lesions of the brain as well as the macrophage rich atherosclerosis, which needs to be confirmed by more AIDS cases with CVA.

高效抗逆转录病毒治疗(HAART)对获得性免疫缺陷综合征(艾滋病)患者的生存产生了重大影响;然而,随着艾滋病患者寿命的延长,艾滋病痴呆复合物(ADC)和其他非艾滋病定义疾病的患病率也在增加,心血管疾病(CVD)也很常见。在haart后时代,这些不同的疾病过程对脑组织中HIV-1 DNA浓度的影响尚未得到彻底评估。本研究的目的是阐明ADC和其他HIV疾病并发症对hart后艾滋病患者大脑病毒载量的影响。我们用定量聚合酶链反应(QPCR)检查了13例死于艾滋病并发症的患者的大脑尸检标本。自1995年以来,除一名患者外,所有患者在死亡前都接受过HAART治疗。2例患者死于严重CVD、全脑多发性脑血管粥样硬化(CVA), 5例患者死于ADC。6例患者无ADC/CVA。采用QPCR检测6个脑组织(脑膜、额叶灰质、额叶白质、颞叶下皮层、小脑和基底神经节)中HIV-1 DNA的存在。在后hart时代,非ADC/CVA患者脑组织中HIV-1 DNA浓度高于ADC患者。在一项新发现中,两名患有严重CVD(尤其是CVA)的患者在脑区也有高浓度的HIV-1,但未表现出与ADC相关的变化。据我们所知,这是首次报道CVA与大脑中HIV-1病毒负荷之间的关系。目前的观察结果表明,抗haart的HIV病毒库可能在大脑ADC病变以及富含巨噬细胞的动脉粥样硬化中存活,这需要更多的CVA艾滋病病例来证实。
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引用次数: 19
Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults. 中国健康成人外周血淋巴细胞亚群参考范围及年龄相关性变化
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0086-4
Yang Jiao, ZhiFeng Qiu, Jing Xie, DongJing Li, TaiSheng Li

This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values. 151 healthy adults aged 19-86 were recruited based on the SENIEUR protocol. Three sets of reference ranges were finally built applicable for the healthy young (19-44 years), middle-aged (45-64 years) and elder adults ([Symbol: see text]65). Comparisons in parameters among the three cohorts showed that a statistically significant increase in CD16CD56+ NK cell was observed between the middle-aged and elder cohorts, whereas for the majority of the parameters, a significant decline was observed between the young and the middle-aged cohorts. Further results showed that inverse correlations were observed between the age and CD19(+) B, CD3(+) T, CD3(+)CD4(+) T, CD4(+)CD45RA(+)CD62L(+) naïve T cell and CD4(+)CD28(+)/CD4(+), while the positive one was identified between the age and the NK cell. These significant changes of the most of immune parameters provided evidence for immunosenescence. Notably, T cell activation markers of CD8(+)CD38(+) and CD8(+)HLA-DR(+) showed reverse trends of association with age, which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.

本研究旨在建立中国健康成人从年轻到老年的外周血淋巴细胞亚群的区域特异性参考范围,并分析淋巴细胞亚群的变化趋势,以评估年龄对该值的影响。根据SENIEUR方案招募了151名19-86岁的健康成年人。最终建立了适用于健康青年(19-44岁)、中年(45-64岁)和老年人([符号:见文]65)的三组参考范围。三个队列的参数比较显示,CD16CD56+ NK细胞在中老年队列中有统计学意义的增加,而大多数参数在青年和中年队列中有统计学意义的下降。进一步结果显示,年龄与CD19(+) B、CD3(+) T、CD3(+)CD4(+) T、CD4(+)CD45RA(+)CD62L(+) naïve T细胞和CD4(+)CD28(+)/CD4(+)呈负相关,而年龄与NK细胞呈正相关。这些显著的免疫参数变化为免疫衰老提供了证据。值得注意的是,T细胞活化标志物CD8(+)、CD38(+)和CD8(+)HLA-DR(+)与年龄呈反向相关趋势,这为进一步研究老年患者矛盾临床表现的机制提供了线索。
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引用次数: 37
Human parthenogenetic embryonic stem cells: one potential resource for cell therapy. 人类孤雌胚胎干细胞:细胞治疗的一种潜在资源。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0096-2
Jie Hao, WanWan Zhu, Chao Sheng, Yang Yu, Qi Zhou

Pluripotent stem cells derived from somatic cells through such processes as nuclear transfer or induced pluripotent stem (iPS) cells present an important model for biomedical research and provide potential resources for cell replacement therapies. However, the overall efficiency of the conversional nuclear transfer is very low and the safety issue remains a major concern for iPS cells. Embryonic stem cells (ESCs) generated from parthenogenetic embryos are one attractive alternative as a source of histocompatible cells and tissues for cell therapy. Recent studies on human parthenogenetic embryonic stem cells (hPG ESCs) have revealed that these ESCs are very similar to the hESCs derived from IVF or in vivo produced blastocysts in gene expression and other characteristics, but full differentiation and development potential of these hPG ESCs have to be further investigated before clinical research and therapeutic interventions. To generate various pluripotent stem cells, diverse reprogramming techniques and approaches will be developed and integrated. This may help elucidate the fundamental mechanisms underlying reprogramming and stem cell biology, and ultimately benefit cell therapy and regenerative medicine.

体细胞通过核移植或诱导多能干细胞(iPS)等过程获得的多能干细胞是生物医学研究的重要模型,为细胞替代疗法提供了潜在资源。然而,转换核转移的整体效率非常低,安全问题仍然是诱导多能干细胞的主要问题。由孤雌生殖胚胎产生的胚胎干细胞(ESCs)作为组织相容性细胞和细胞治疗组织的来源是一个有吸引力的选择。最近对人类孤雌胚胎干细胞(hPG ESCs)的研究表明,这些ESCs在基因表达等特征上与体外受精或体内产生的囊胚hESCs非常相似,但在临床研究和治疗干预之前,这些hPG ESCs的充分分化和发育潜力有待进一步研究。为了产生多种多能干细胞,各种重编程技术和方法将被开发和整合。这可能有助于阐明重编程和干细胞生物学的基本机制,并最终有益于细胞治疗和再生医学。
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引用次数: 34
Mesenchymal stem cells targeting the GVHD. 靶向GVHD的间充质干细胞。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0091-7
Liang Wang, Robert ChunHua Zhao

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. About 35%-50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. It is associated with considerable morbidity and mortality, particularly in patients who do not respond to primary therapy, which usually consists of glucocorticoids(steroids). Most of the available second-line and third-line treatments for steroid-refractory acute GVHD induce severe immunodeficiency, which is commonly accompanied by lethal infectious complications. Mesenchymal stem cells (MSCs) have been shown to mediate immunomodulatory effects. The recently elucidated immunosuppressive potential of mesenchymal stem cells has set the stage for their clinical testing as cellular immunosuppressants, MSCs have been used in patients with steroid-refractory acute GVHD, and encouraging responses have been obtained in many studies. The utility of MSCs for the treatment of GVHD is becoming clear.

急性移植物抗宿主病(GVHD)发生在同种异体造血干细胞移植后,是供体免疫细胞对宿主组织的反应。大约35%-50%的造血干细胞移植(HSCT)受者会发展为急性GVHD。它与相当高的发病率和死亡率有关,特别是对通常由糖皮质激素(类固醇)组成的初级治疗无反应的患者。大多数可用的二线和三线治疗类固醇难治性急性GVHD诱导严重免疫缺陷,这通常伴随着致命的感染并发症。间充质干细胞(MSCs)已被证明具有介导免疫调节作用。最近阐明的间充质干细胞的免疫抑制潜力为其作为细胞免疫抑制剂的临床试验奠定了基础,间充质干细胞已被用于治疗类固醇难治性急性GVHD患者,并在许多研究中获得了令人鼓舞的反应。间充质干细胞在治疗GVHD方面的作用越来越明显。
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引用次数: 14
Effects of chemical activation and season on birth efficiency of cloned pigs. 化学活化和季节对克隆猪产仔效率的影响。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0087-3
YuFang Ma, Yan Li, HengXi Wei, QiuYan Li, Rui Fang, Rui Zhao, Kun Zhang, Kai Xue, YanKun Lou, YunPing Dai, LinSheng Lian, Ning Li

The effects of chemical activation on birth efficiency of cloned pigs were studied by investigating the developmental process from porcine oocyte activation to birth of cloned pigs. Three different activation methods were used: (i) Electroporation (Ele); (ii) Ele followed by incubation with 6-dimethylaminopurine (6-DMAP); and (iii) Ele followed by a treatment with cycloheximide (CHX). In experiment 1, the rates of cleavage, developmental rates and cell number of porcine parthenogenetic (PA) embryos were investigated in the three treatment groups. In experiment 2, NT embryos produced by the three different activation treatments were compared for the rates of cleavage, development and cell number. Finally, the effects of Ele and Ele+CHX activation methods on birth efficiency of cloned pigs were compared. The activated oocytes treated by combination activation generally showed a higher (P<0.05) blastocyst rate and produced more expanded blastocysts than oocytes activated with Ele. The rates of cleavage and total cell number of parthenotes were not significantly different. Parthenogenetic embryos activated with 6-DMAP developed into blastocyst and expanded blastocyst stages at a significantly (P<0.05) higher rate than those treated with Ele, but the developmental capability was dramatically decreased in NT embryos. With the CHX activation method, the NT embryo blastocyst rate was substantially (P<0.05) increased although the production of expanded blastocysts was not significantly different from that by the other two methods. The birth rate of cloned pigs increased in the CHX group, though the rate was not significantly different from Ele. The effects of season on developmental rate of the porcine PA embryos and birth rate of cloned pigs were also examined in our study. Porcine oocytes collected in the spring had higher developmental capabilities than those collected in the winter. However, no difference in birth rate of the cloned pigs was found between the oocytes collected in the two seasons. The results obtained from PA and NT embryos, following different activation methods, were inconsistent, suggesting that activation mechanisms are dissimilar in PA and NT embryos. Although the chemical activation in our study leads to an elevation of the blastocyst rate, it does not improve the oocyte's molecular programming and so does not significantly improve the efficiency of producing cloned pig births.

通过研究猪卵母细胞活化到克隆猪出生的发育过程,研究化学活化对克隆猪出生效率的影响。采用三种不同的活化方法:(1)电穿孔(Ele);(ii)用6-二甲氨基嘌呤(6-DMAP)孵育;(iii) Ele,然后用环己亚胺(CHX)处理。试验1观察3个处理组猪孤雌生殖胚胎的卵裂率、发育率和细胞数。实验2比较了三种不同活化处理产生的NT胚的卵裂率、发育率和细胞数。最后比较了Ele和Ele+CHX激活方式对克隆猪产仔效率的影响。经联合活化处理的活化卵母细胞总体上表现出较高的(P
{"title":"Effects of chemical activation and season on birth efficiency of cloned pigs.","authors":"YuFang Ma,&nbsp;Yan Li,&nbsp;HengXi Wei,&nbsp;QiuYan Li,&nbsp;Rui Fang,&nbsp;Rui Zhao,&nbsp;Kun Zhang,&nbsp;Kai Xue,&nbsp;YanKun Lou,&nbsp;YunPing Dai,&nbsp;LinSheng Lian,&nbsp;Ning Li","doi":"10.1007/s11427-009-0087-3","DOIUrl":"https://doi.org/10.1007/s11427-009-0087-3","url":null,"abstract":"<p><p>The effects of chemical activation on birth efficiency of cloned pigs were studied by investigating the developmental process from porcine oocyte activation to birth of cloned pigs. Three different activation methods were used: (i) Electroporation (Ele); (ii) Ele followed by incubation with 6-dimethylaminopurine (6-DMAP); and (iii) Ele followed by a treatment with cycloheximide (CHX). In experiment 1, the rates of cleavage, developmental rates and cell number of porcine parthenogenetic (PA) embryos were investigated in the three treatment groups. In experiment 2, NT embryos produced by the three different activation treatments were compared for the rates of cleavage, development and cell number. Finally, the effects of Ele and Ele+CHX activation methods on birth efficiency of cloned pigs were compared. The activated oocytes treated by combination activation generally showed a higher (P<0.05) blastocyst rate and produced more expanded blastocysts than oocytes activated with Ele. The rates of cleavage and total cell number of parthenotes were not significantly different. Parthenogenetic embryos activated with 6-DMAP developed into blastocyst and expanded blastocyst stages at a significantly (P<0.05) higher rate than those treated with Ele, but the developmental capability was dramatically decreased in NT embryos. With the CHX activation method, the NT embryo blastocyst rate was substantially (P<0.05) increased although the production of expanded blastocysts was not significantly different from that by the other two methods. The birth rate of cloned pigs increased in the CHX group, though the rate was not significantly different from Ele. The effects of season on developmental rate of the porcine PA embryos and birth rate of cloned pigs were also examined in our study. Porcine oocytes collected in the spring had higher developmental capabilities than those collected in the winter. However, no difference in birth rate of the cloned pigs was found between the oocytes collected in the two seasons. The results obtained from PA and NT embryos, following different activation methods, were inconsistent, suggesting that activation mechanisms are dissimilar in PA and NT embryos. Although the chemical activation in our study leads to an elevation of the blastocyst rate, it does not improve the oocyte's molecular programming and so does not significantly improve the efficiency of producing cloned pig births.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"657-64"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0087-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Characterization of GLUT4-containing vesicles in 3T3-L1 adipocytes by total internal reflection fluorescence microscopy. 用全内反射荧光显微镜观察3T3-L1脂肪细胞中含glut4的囊泡。
Pub Date : 2009-07-01 Epub Date: 2009-07-30 DOI: 10.1007/s11427-009-0081-9
Yan Wang, JinZhong Zhang, Yu Chen, Li Jiang, Wei Ji, Tao Xu

Insulin-responsive GLUT4 (glucose transporter 4) translocation plays a major role in regulating glucose uptake in adipose tissue and muscle. Whether or not there is a specialized secretory GSV (GLUT4 storage vesicle) pool, and more importantly how GSVs are translocated to the PM (plasma membrane) under insulin stimulation is still under debate. In the present study, we systematically analyzed the dynamics of a large number of single GLUT4-containing vesicles in 3T3-L1 adipocytes by TIRFM (total internal reflection fluorescence microscopy). We found that GLUT4-containing vesicles can be classified into three groups according to their mobility, namely vertical, stable, and lateral GLUT4-containing vesicles. Among these groups, vertical GLUT4-containing vesicles exclude transferrin receptors and move towards the PM specifically in response to insulin stimulation, while stable and lateral GLUT4-containing vesicles contain transferrin receptors and show no insulin responsiveness. These data demonstrate that vertical GLUT4-containing vesicles correspond to specialized secretory GSVs, which approach the PM directly and bypass the constitutive recycling pathway.

胰岛素反应性GLUT4(葡萄糖转运蛋白4)易位在调节脂肪组织和肌肉的葡萄糖摄取中起主要作用。是否存在一个专门的分泌GSV (GLUT4储存囊泡)池,更重要的是GSV在胰岛素刺激下如何转运到PM(质膜),目前仍有争议。在本研究中,我们采用全内反射荧光显微镜(TIRFM)系统分析了3T3-L1脂肪细胞中大量单个含glut4的囊泡的动态。我们发现,根据其流动性,含glut4的囊泡可分为三组,即垂直、稳定和侧向含glut4的囊泡。在这些组中,垂直的含glut4的小泡排除转铁蛋白受体,并在胰岛素刺激下特异性地向PM移动,而稳定的和侧向的含glut4的小泡含有转铁蛋白受体,不表现出胰岛素反应。这些数据表明,垂直的含glut4的囊泡对应于专门的分泌性GSVs,它们直接接近PM并绕过本构循环途径。
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引用次数: 8
东亚飞蝗 hunchback 基因在卵子形成和胚胎发育过程中的原位表达 东亚飞蝗 hunchback 基因在卵子形成和胚胎发育过程中的原位表达
Pub Date : 2009-06-20 DOI: 10.1360/ZC2009-39-6-559
何正波, 陈斌, 曹月青, 蔡志华, 冯国忠, 李廷景, 夏玉先
hb ( hunchback )基因是昆虫胚胎前后轴模式形成的关键基因. 对东亚飞蝗( Locusta migratoria manilensis , Meyen)hb基因的功能已有报道, 但其表达模式还不清楚. 为了研究hb基因在东亚飞蝗卵子形成和胚胎发育过程中的时空表达情况, 本研究采用免疫组化方法在蛋白质水平上检测了hb基因的时空表达模式. 在卵子形成过程中, hb基因局限在卵细胞核区中表达, 随着卵子的发育逐渐移至卵细胞的后端; 卵受精后, 核区里的Hb蛋白向外扩散, 在卵后端形成浓度梯度; 胚盘期, hb 基因在胚盘中央呈带状表达; 胚盘分化为原头和原躯干后, 表达条带变宽, 并呈现出梯度表达, 该表达区域将形成颌、胸部的部分体节; 随着腹节开始形成, hb基因在颌胸部的表达逐渐减弱, 而在腹部后端的“生长区”表达, 并呈现出不连续性. 经比较, hb基因在昆虫颌胸部的表达较为保守, 而在卵子形成过程中和腹部的表达具有较大的变异性. 与黑腹果蝇等长胚带昆虫相比, 东亚飞蝗 hb 基因在体节形成的基因级联调控中具有更重要、更直接的调控作用.
hb ( hunchback )基因是昆虫胚胎前后轴模式形成的关键基因. 对东亚飞蝗( Locusta migratoria manilensis , Meyen)hb基因的功能已有报道, 但其表达模式还不清楚. 为了研究hb基因在东亚飞蝗卵子形成和胚胎发育过程中的时空表达情况, 本研究采用免疫组化方法在蛋白质水平上检测了hb基因的时空表达模式. 在卵子形成过程中, hb基因局限在卵细胞核区中表达, 随着卵子的发育逐渐移至卵细胞的后端; 卵受精后, 核区里的Hb蛋白向外扩散, 在卵后端形成浓度梯度; 胚盘期, hb 基因在胚盘中央呈带状表达; 胚盘分化为原头和原躯干后, 表达条带变宽, 并呈现出梯度表达, 该表达区域将形成颌、胸部的部分体节; 随着腹节开始形成, hb基因在颌胸部的表达逐渐减弱, 而在腹部后端的“生长区”表达, 并呈现出不连续性. 经比较, hb基因在昆虫颌胸部的表达较为保守, 而在卵子形成过程中和腹部的表达具有较大的变异性. 与黑腹果蝇等长胚带昆虫相比, 东亚飞蝗 hb 基因在体节形成的基因级联调控中具有更重要、更直接的调控作用.
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引用次数: 0
Towards transgenic primates: What can we learn from mouse genetics? 迈向转基因灵长类动物:我们能从小鼠遗传学中学到什么?
Pub Date : 2009-06-01 Epub Date: 2009-06-26 DOI: 10.1007/s11427-009-0082-8
Hui KUANG, Phillip L WANG, Joe Z TSIEN

Considering the great physiological and behavioral similarities with humans, monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the preclinical research and development of novel therapeutics for treating human diseases. Various powerful genetic technologies initially developed for making mouse models are being explored for generating transgenic primate models. We review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates.

考虑到与人类在生理和行为上的巨大相似性,猴子不仅是研究复杂认知行为的理想模型,也是治疗人类疾病的新疗法的临床前研究和开发的理想模型。各种强大的基因技术最初开发用于制造小鼠模型正在探索产生转基因灵长类动物模型。本文综述了最新的基因工程技术,讨论了系统生产转基因灵长类动物的潜力和局限性。
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引用次数: 4
The CXXC finger 5 protein is required for DNA damage-induced p53 activation. CXXC指5蛋白是DNA损伤诱导的p53激活所必需的。
Pub Date : 2009-06-01 Epub Date: 2009-06-26 DOI: 10.1007/s11427-009-0083-7
Min ZHANG, RuiPeng WANG, YanYi WANG, FeiCi DIAO, Fei LU, Dong GAO, DanYing CHEN, ZhongHe ZHAI, HongBing SHU

The tumor suppressor p53 is a critical component of the DNA damage response pathway that induces a set of genes responsible for cell cycle arrest, senescence, apoptosis, and DNA repair. The ataxia telangiectasia mutated protein kinase (ATM) responds to DNA-damage stimuli and signals p53 stabilization and activation, thereby facilitating transactivation of p53 inducible genes and maintainence of genome integrity. In this study, we identified a CXXC zinc finger domain containing protein termed CF5 as a critical component in the DNA damage signaling pathway. CF5 induces p53 transcriptional activity and apoptosis in cells expressing wild type p53 but not in p53-deficient cells. Knockdown of CF5 inhibits DNA damage-induced p53 activation as well as cell cycle arrest. Furthermore, CF5 physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin. These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage.

肿瘤抑制因子p53是DNA损伤反应通路的关键组成部分,该通路诱导一系列负责细胞周期阻滞、衰老、凋亡和DNA修复的基因。共济失调毛细血管扩张突变蛋白激酶(ataxia telangi扩张mutatated protein kinase, ATM)响应dna损伤刺激,发出p53稳定和激活的信号,从而促进p53诱导基因的转激活,维持基因组完整性。在这项研究中,我们发现了一种CXXC锌指结构域,它含有一种称为CF5的蛋白质,是DNA损伤信号通路的关键成分。CF5在表达野生型p53的细胞中诱导p53的转录活性和凋亡,而在p53缺陷型细胞中无此作用。敲低CF5抑制DNA损伤诱导的p53激活以及细胞周期阻滞。此外,CF5物理上与ATM相互作用,并且是DNA损伤诱导的ATM磷酸化所必需的,而不是其在染色质上的募集。这些发现表明,CF5在响应DNA损伤的ATM-p53信号传导中起着至关重要的作用。
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引用次数: 28
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