Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Current progress and prospects of induced pluripotent stem cells.","authors":"LingYi Chen, Lin Liu","doi":"10.1007/s11427-009-0092-6","DOIUrl":"https://doi.org/10.1007/s11427-009-0092-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"622-36"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0092-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337687","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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"High level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDS.","authors":"Li Zhao, Derek C Galligan, Susanna L Lamers, Stephanie Yu, Lamia Shagrun, Marco Salemi, Michael S McGrath","doi":"10.1007/s11427-009-0085-5","DOIUrl":"https://doi.org/10.1007/s11427-009-0085-5","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"651-6"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0085-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337690","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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults.","authors":"Yang Jiao, ZhiFeng Qiu, Jing Xie, DongJing Li, TaiSheng Li","doi":"10.1007/s11427-009-0086-4","DOIUrl":"https://doi.org/10.1007/s11427-009-0086-4","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"643-50"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0086-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337689","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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Human parthenogenetic embryonic stem cells: one potential resource for cell therapy.","authors":"Jie Hao, WanWan Zhu, Chao Sheng, Yang Yu, Qi Zhou","doi":"10.1007/s11427-009-0096-2","DOIUrl":"https://doi.org/10.1007/s11427-009-0096-2","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"599-602"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0096-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337204","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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Mesenchymal stem cells targeting the GVHD.","authors":"Liang Wang, Robert ChunHua Zhao","doi":"10.1007/s11427-009-0091-7","DOIUrl":"https://doi.org/10.1007/s11427-009-0091-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"603-9"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0091-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337205","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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Effects of chemical activation and season on birth efficiency of cloned pigs.","authors":"YuFang Ma, Yan Li, HengXi Wei, QiuYan Li, Rui Fang, Rui Zhao, Kun Zhang, Kai Xue, YanKun Lou, YunPing Dai, LinSheng Lian, 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}
Pub Date : 2009-07-01Epub Date: 2009-07-30DOI: 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.
{"title":"Characterization of GLUT4-containing vesicles in 3T3-L1 adipocytes by total internal reflection fluorescence microscopy.","authors":"Yan Wang, JinZhong Zhang, Yu Chen, Li Jiang, Wei Ji, Tao Xu","doi":"10.1007/s11427-009-0081-9","DOIUrl":"https://doi.org/10.1007/s11427-009-0081-9","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 7","pages":"665-71"},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0081-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28337692","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}
Pub Date : 2009-06-01Epub Date: 2009-06-26DOI: 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.
{"title":"Towards transgenic primates: What can we learn from mouse genetics?","authors":"Hui KUANG, Phillip L WANG, Joe Z TSIEN","doi":"10.1007/s11427-009-0082-8","DOIUrl":"https://doi.org/10.1007/s11427-009-0082-8","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 6","pages":"506-14"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0082-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28268305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-06-01Epub Date: 2009-06-26DOI: 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。
{"title":"The CXXC finger 5 protein is required for DNA damage-induced p53 activation.","authors":"Min ZHANG, RuiPeng WANG, YanYi WANG, FeiCi DIAO, Fei LU, Dong GAO, DanYing CHEN, ZhongHe ZHAI, HongBing SHU","doi":"10.1007/s11427-009-0083-7","DOIUrl":"https://doi.org/10.1007/s11427-009-0083-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49127,"journal":{"name":"Science in China. Series C, Life Sciences / Chinese Academy of Sciences","volume":"52 6","pages":"528-38"},"PeriodicalIF":0.0,"publicationDate":"2009-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11427-009-0083-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28268308","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}