Introducing a combination of transcription factors such as Oct4,Sox2,Klf4 and c-Myc（OSKM）enables reprogramming which converts somatic cells into induced pluripotent stem cells（i PSCs）（Takahashi and Yamanaka,2006...Introducing a combination of transcription factors such as Oct4,Sox2,Klf4 and c-Myc（OSKM）enables reprogramming which converts somatic cells into induced pluripotent stem cells（i PSCs）（Takahashi and Yamanaka,2006）.i PSCs play an important role in clinical and regenerative medicine because they can be utilized to model a specific disease or differentiate into functional cells for transplantation.Enhancing the efficiency of induction and improving the qualities of iPSCs are constant themes in this field.展开更多
Pluripotency-associated factors and their rivals, lineage specifiers, have long been consid- ered the determining factors for the identity of pluripotent and differentiated cells, respectively. Therefore, factors that...Pluripotency-associated factors and their rivals, lineage specifiers, have long been consid- ered the determining factors for the identity of pluripotent and differentiated cells, respectively. Therefore, factors that are employed for cellular reprogramming in order to induce pluripotency have been identified mainly from embryonic stem cell （ESC）-enriched and pluripotency-associated factors. Recently, lineage specifiers have been identified to play important roles in orchestrating the process of restoring pluripotency. In this review, we summarize the latest discoveries regarding cell fate conversion using pluripotency-associated factors and lineage specifiers. We highlight the value of the ＂seesaw＂ model in defining cellular identity, opening up a novel scenario to consider pluri- potency and lineage specification.展开更多
Around 400 million people worldwide suffer from diabetes mellitus.The major pathological event for Type 1 diabetes and advanced Type 2 diabetes is loss or impairment of insulin-secreting β cells of the pancreas.For t...Around 400 million people worldwide suffer from diabetes mellitus.The major pathological event for Type 1 diabetes and advanced Type 2 diabetes is loss or impairment of insulin-secreting β cells of the pancreas.For the past 100 years,daily insulin injection has served as a life-saving treatment for these patients.However,insulin injection often cannot achieve full glucose control,and over time poor glucose control leads to severe complications and mortality.As an alternative treatment,islet transplantation has been demonstrated to effectively maintain glucose homeostasis in diabetic patients,but its wide application is limited by the scarcity of donated islets.Therefore,it is important to define new strategies to obtain functional human β cells for transplantation therapies.Here,we summarize recent progress towards the production of β cells in vitro from pluripotent stem cells or somatic cell types including a cells,pancreatic exocrine cells,gastrointestinal stem cells,fibroblasts and hepatocytes.We also discuss novel methods for optimizing β cell transplantation and maintenance in vivo.From our perspective,the future of βcell replacement therapy is very promising although it is still challenging to control differentiation of β cells in vitro and to protect these cells from autoimmune attack in Type 1 diabetic patients.Overall,tremendous progress has been made in understanding βcell differentiation and producing functional β cells with different methods.In the coming years,we believe more clinical trials will be launched to move these technologies towards treatments to benefit diabetic patients.展开更多
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDA01020102)the grant from the Natural Science Foundation of China (No. 81225004)
文摘Introducing a combination of transcription factors such as Oct4,Sox2,Klf4 and c-Myc（OSKM）enables reprogramming which converts somatic cells into induced pluripotent stem cells（i PSCs）（Takahashi and Yamanaka,2006）.i PSCs play an important role in clinical and regenerative medicine because they can be utilized to model a specific disease or differentiate into functional cells for transplantation.Enhancing the efficiency of induction and improving the qualities of iPSCs are constant themes in this field.
基金supported by the National Basic Research Program of China(973 Program,Grant No.2012CB966401)the Key New Drug Creation and Manufacturing Program(Grant No.2011ZX09102-010-03)+1 种基金the National Science and Technology Major Project(Grant No.2013ZX10001003)the Ministry of Science and Technology(Grant No.2011DFA30730 and 2013DFG30680)and 111 Project
文摘Pluripotency-associated factors and their rivals, lineage specifiers, have long been consid- ered the determining factors for the identity of pluripotent and differentiated cells, respectively. Therefore, factors that are employed for cellular reprogramming in order to induce pluripotency have been identified mainly from embryonic stem cell （ESC）-enriched and pluripotency-associated factors. Recently, lineage specifiers have been identified to play important roles in orchestrating the process of restoring pluripotency. In this review, we summarize the latest discoveries regarding cell fate conversion using pluripotency-associated factors and lineage specifiers. We highlight the value of the ＂seesaw＂ model in defining cellular identity, opening up a novel scenario to consider pluri- potency and lineage specification.
文摘Around 400 million people worldwide suffer from diabetes mellitus.The major pathological event for Type 1 diabetes and advanced Type 2 diabetes is loss or impairment of insulin-secreting β cells of the pancreas.For the past 100 years,daily insulin injection has served as a life-saving treatment for these patients.However,insulin injection often cannot achieve full glucose control,and over time poor glucose control leads to severe complications and mortality.As an alternative treatment,islet transplantation has been demonstrated to effectively maintain glucose homeostasis in diabetic patients,but its wide application is limited by the scarcity of donated islets.Therefore,it is important to define new strategies to obtain functional human β cells for transplantation therapies.Here,we summarize recent progress towards the production of β cells in vitro from pluripotent stem cells or somatic cell types including a cells,pancreatic exocrine cells,gastrointestinal stem cells,fibroblasts and hepatocytes.We also discuss novel methods for optimizing β cell transplantation and maintenance in vivo.From our perspective,the future of βcell replacement therapy is very promising although it is still challenging to control differentiation of β cells in vitro and to protect these cells from autoimmune attack in Type 1 diabetic patients.Overall,tremendous progress has been made in understanding βcell differentiation and producing functional β cells with different methods.In the coming years,we believe more clinical trials will be launched to move these technologies towards treatments to benefit diabetic patients.
