Aging is a major concern in developing societies, which are characterized by an escalation in the aged population as well as in the prevalence of many chronic diseases associated with this inevitable biological process. There is a strong desire to delay aging and increase the length of disease-free life. For that purpose there is a need to better understand the human aging process, as the mechanisms that regulate aging remain largely unknown. The adult stem cell reservoir, which not only declines in size with age, but also particularly handicaps those regenerative tissues repopulated by this reservoir of stem cells, deserves special consideration. We have recently reported the characterization of a new stem cell human experimental model, based on posttranslational defects of the LMNA gene expression associated with progeroid syndromes. In this work, we summarize the necessity of developing reliable human experimental models for the study of human stem cell aging, and outline the phenotypes exhibited by this new experimental human aging model due to accumulation of an aberrant LMNA product with detrimental repercussions to in vivo functionality. This in vitro model has been fundamental for the identification of a novel role of a known transcription factor in human stem cell aging, demonstrating the potential of the model as a tool to unravel the molecular mechanisms governing human aging.
{"title":"A human experimental model of laminopathy based on adult stem cells establishes the relevance of Oct1 transcription factor in the aging process","authors":"A. Infante, A. Gago, C. I. Rodríguez","doi":"10.14800/SCTI.276","DOIUrl":"https://doi.org/10.14800/SCTI.276","url":null,"abstract":"Aging is a major concern in developing societies, which are characterized by an escalation in the aged population as well as in the prevalence of many chronic diseases associated with this inevitable biological process. There is a strong desire to delay aging and increase the length of disease-free life. For that purpose there is a need to better understand the human aging process, as the mechanisms that regulate aging remain largely unknown. The adult stem cell reservoir, which not only declines in size with age, but also particularly handicaps those regenerative tissues repopulated by this reservoir of stem cells, deserves special consideration. We have recently reported the characterization of a new stem cell human experimental model, based on posttranslational defects of the LMNA gene expression associated with progeroid syndromes. In this work, we summarize the necessity of developing reliable human experimental models for the study of human stem cell aging, and outline the phenotypes exhibited by this new experimental human aging model due to accumulation of an aberrant LMNA product with detrimental repercussions to in vivo functionality. This in vitro model has been fundamental for the identification of a novel role of a known transcription factor in human stem cell aging, demonstrating the potential of the model as a tool to unravel the molecular mechanisms governing human aging.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657811","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}
Human acute myeloid leukemia (AML) derives from rare leukemic stem cells (LSCs). Relapse of disease can be ascribed to LSCs to some degree. Currently, a number of surface markers of AML LSCs have been identified, including CD123, CD44, CLL-1, CD96, CD47, CD32, CD25 and TIM-3. Moreover, monoclonal antibodies targeting some markers have demonstrated efficacy in xenotransplantation models. In our recent work, we found that N-cadherin and Tie2 positive CD34 + CD38 - CD123 + populations could develop acute myeloid leukemia more effectively in NOD/SCID mice than their negative counterparts at the same doses. Meanwhile, the blast cells from the bone marrow of leukemic mice are transplantable. It is speculated that FLT3-ITD mutation could make the LSCs more capable of expanding in the environment. These data suggested that N-cadherin and Tie2 were very important in development of leukemia as LSC markers.
{"title":"New insight of leukemic stem cell","authors":"S. Qiu, Ming Wang, Jianxiang Wang","doi":"10.14800/SCTI.178","DOIUrl":"https://doi.org/10.14800/SCTI.178","url":null,"abstract":"Human acute myeloid leukemia (AML) derives from rare leukemic stem cells (LSCs). Relapse of disease can be ascribed to LSCs to some degree. Currently, a number of surface markers of AML LSCs have been identified, including CD123, CD44, CLL-1, CD96, CD47, CD32, CD25 and TIM-3. Moreover, monoclonal antibodies targeting some markers have demonstrated efficacy in xenotransplantation models. In our recent work, we found that N-cadherin and Tie2 positive CD34 + CD38 - CD123 + populations could develop acute myeloid leukemia more effectively in NOD/SCID mice than their negative counterparts at the same doses. Meanwhile, the blast cells from the bone marrow of leukemic mice are transplantable. It is speculated that FLT3-ITD mutation could make the LSCs more capable of expanding in the environment. These data suggested that N-cadherin and Tie2 were very important in development of leukemia as LSC markers.","PeriodicalId":90974,"journal":{"name":"Stem cell and translational investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657764","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}
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