The regulation of gene expression by microRNAs(miRNAs)is a recently discovered pattern of gene regulation in animals and plants.MiRNAs have been implicated in various aspects of animal development and cell differentia...The regulation of gene expression by microRNAs(miRNAs)is a recently discovered pattern of gene regulation in animals and plants.MiRNAs have been implicated in various aspects of animal development and cell differentiation,such as early embryonic development,neuronal development,muscle development,and lymphocyte development,by the analysis of genetic deletions of individual miRNAs in mammals.These studies show that miRNAs are key regulators in animal development and are potential causes of human diseases.Here we review some recent discoveries about the functions of miRNAs in cell differentiation and development.展开更多
Increasing evidence indicates a role of leptin in immune response, but it remains largely unclear whether leptin signaling is involved in regulating NK cell development in the bone marrow （BM）. In this study, we hav...Increasing evidence indicates a role of leptin in immune response, but it remains largely unclear whether leptin signaling is involved in regulating NK cell development in the bone marrow （BM）. In this study, we have characterized NK cell differentiation and maturation in the BM of leptin-receptor deficient db/db mice at a prediabetic stage. Although the BM cellularity was similar to the control value, the total number of NK cells was severely reduced in mutant mice. Flow cytometric analysis of db/db BM cells revealed significantly decreased frequencies of developing NK cells at various stages of differentiation. BM db/db NK cells displayed markedly increased apoptosis but maintained normal cell cycling status and proliferative capacity. Moreover, recombinant leptin could significantly enhance the survival of NK cells from wild-type mice in cultures. Further examination on NK cell functional activity showed that db/db NK cells exhibited normal intrinsic cytotoxicity with significantly increased IL-10 production. Taken together, our findings suggest that leptin signaling regulates NK cell development via enhancing the survival of immature NK cells in mouse BM.展开更多
Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additio...Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additional isoforms from each of the five homologous genes in the family. The functional forms of Ikaros proteins could be even more diverse due to protein–protein interactions readily established between family members. Emerging evidence suggests that targeting Ikaros proteins is feasible and effective in therapeutic applications, although the exact roles of Ikaros proteins remain elusive within the intricate regulatory networks in which they are involved. In this review we collect existing knowledge as to the functions, regulatory pathways, and molecular mechanisms of this family of proteins in an attempt to gain a better understanding through the comparison of activities and interactions among family members.展开更多
All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)do...All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)does not only exist as a membranebound form but is also found as a soluble protein in human serum.2,3 The exact role of soluble IL-7Rα(sIL-7Rα)proteins remains to be determined.However,increased amounts of sIL-7Rαhave been associated with an increased risk of inflammation and autoimmunity.3,4 Mechanistically,sIL-7Rαproteins can be generated by alternative splicing of Il7r gene transcripts that encode IL-7Rα.Curiously,however,such Il7r splice isoforms have only been described in humans and have never been described in mice.5 Consequently,the importance of Il7r alternative splice products that are not conserved across species has remained questionable.展开更多
基金Supported by National Key Basic Research and Development Program of China(Grant No.2005CB724602)Knowledge Innovation Project of the Chinese Academy of Sciences(Grant Nos.KSCX2-YW-R-096,KSCX1-YW-R-64)
文摘The regulation of gene expression by microRNAs(miRNAs)is a recently discovered pattern of gene regulation in animals and plants.MiRNAs have been implicated in various aspects of animal development and cell differentiation,such as early embryonic development,neuronal development,muscle development,and lymphocyte development,by the analysis of genetic deletions of individual miRNAs in mammals.These studies show that miRNAs are key regulators in animal development and are potential causes of human diseases.Here we review some recent discoveries about the functions of miRNAs in cell differentiation and development.
文摘Increasing evidence indicates a role of leptin in immune response, but it remains largely unclear whether leptin signaling is involved in regulating NK cell development in the bone marrow （BM）. In this study, we have characterized NK cell differentiation and maturation in the BM of leptin-receptor deficient db/db mice at a prediabetic stage. Although the BM cellularity was similar to the control value, the total number of NK cells was severely reduced in mutant mice. Flow cytometric analysis of db/db BM cells revealed significantly decreased frequencies of developing NK cells at various stages of differentiation. BM db/db NK cells displayed markedly increased apoptosis but maintained normal cell cycling status and proliferative capacity. Moreover, recombinant leptin could significantly enhance the survival of NK cells from wild-type mice in cultures. Further examination on NK cell functional activity showed that db/db NK cells exhibited normal intrinsic cytotoxicity with significantly increased IL-10 production. Taken together, our findings suggest that leptin signaling regulates NK cell development via enhancing the survival of immature NK cells in mouse BM.
文摘Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additional isoforms from each of the five homologous genes in the family. The functional forms of Ikaros proteins could be even more diverse due to protein–protein interactions readily established between family members. Emerging evidence suggests that targeting Ikaros proteins is feasible and effective in therapeutic applications, although the exact roles of Ikaros proteins remain elusive within the intricate regulatory networks in which they are involved. In this review we collect existing knowledge as to the functions, regulatory pathways, and molecular mechanisms of this family of proteins in an attempt to gain a better understanding through the comparison of activities and interactions among family members.
基金supported by the Intramural Research Program of the US National Institutes of Health,the National Cancer Institute,the Center for Cancer Researchthe Financial Support Project,Long-Term Overseas Dispatch,Tenure-Track Faculty,Pusan National University.
文摘All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)does not only exist as a membranebound form but is also found as a soluble protein in human serum.2,3 The exact role of soluble IL-7Rα(sIL-7Rα)proteins remains to be determined.However,increased amounts of sIL-7Rαhave been associated with an increased risk of inflammation and autoimmunity.3,4 Mechanistically,sIL-7Rαproteins can be generated by alternative splicing of Il7r gene transcripts that encode IL-7Rα.Curiously,however,such Il7r splice isoforms have only been described in humans and have never been described in mice.5 Consequently,the importance of Il7r alternative splice products that are not conserved across species has remained questionable.
