Integrin, a heterodimeric adhesive molecule composed of a and (5 subunits, can regulate cell adhesion and trafficking. Recent data have documented that, at the 'implantation window' stage, aVp3 integrin partic...Integrin, a heterodimeric adhesive molecule composed of a and (5 subunits, can regulate cell adhesion and trafficking. Recent data have documented that, at the 'implantation window' stage, aVp3 integrin participates in the maternal-fetal interaction and becomes a potential marker of uterine receptivity. Furthermore, it can affect invasiveness of embryo. This work made a further study about its action mechanism. Results of indirect immunofluorescence and laser scanning confocal microscopy showed that αVβ3 integrin was clearly expressed in the mouse blastocyst. Injection of αVβS integrin antiserum into a uterine horn of a pregnant mouse on day 3 markedly decreased the number of embryos implanted (P 【 0.001). In a co-culture model, aVp3 integrin antisera at 1 : 100 and 1 : 200 dilutions significantly depressed the attachment and outgrowth reactions of blastocysts on monolayer of uterine epithelial cells. Analysis of correlation manifested that the inhibitory effect of αVβ3 integrin antiserum was展开更多
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays a critical role in angiogenesis. Recent reports indicated that VEGF was closely involved in embryo implantation and embryoni...Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays a critical role in angiogenesis. Recent reports indicated that VEGF was closely involved in embryo implantation and embryonic vasculogenesis. However, very little information is available about the detailed expression and function of VEGF at implantation 'window'. In this work, VEGFs were primarily present on uterine epithelial cell monolayer and blasto-cysts including the outgrew trophoblasts at implantation window. VEGF antibodies decreased the number of mice embryos implanted and the percentage of blastocysts with attachment and outgrowth in a co-culture model in a dose-dependant manner. These findings demonstrate that VEGF is one of the essential cytokines for embryo implantation in mouse. VEGF may act as a local mediator to regulate the maternal-fetal interaction, and facilitate blastocyst implantation.展开更多
CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function.More rec...CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function.More recently,this technology has been increasingly applied to the study or treatment of human diseases,including Barth syndrome effects on the heart,Duchenne muscular dystrophy,hemophilia,b-Thalassemia,and cystic fibrosis.CRISPR/Cas9(CRISPR-associated protein 9)genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo.In addition to genetic diseases,CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5,the programmed death 1 gene,or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome(AIDS)or promoting anti-tumor immunotherapy.Furthermore,this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials,including molecules,cells or organs,on a large scale.Finally,CRISPR/Cas9 has been teamed with induced pluripotent stem(iPS)cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation.This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.展开更多
文摘Integrin, a heterodimeric adhesive molecule composed of a and (5 subunits, can regulate cell adhesion and trafficking. Recent data have documented that, at the 'implantation window' stage, aVp3 integrin participates in the maternal-fetal interaction and becomes a potential marker of uterine receptivity. Furthermore, it can affect invasiveness of embryo. This work made a further study about its action mechanism. Results of indirect immunofluorescence and laser scanning confocal microscopy showed that αVβ3 integrin was clearly expressed in the mouse blastocyst. Injection of αVβS integrin antiserum into a uterine horn of a pregnant mouse on day 3 markedly decreased the number of embryos implanted (P 【 0.001). In a co-culture model, aVp3 integrin antisera at 1 : 100 and 1 : 200 dilutions significantly depressed the attachment and outgrowth reactions of blastocysts on monolayer of uterine epithelial cells. Analysis of correlation manifested that the inhibitory effect of αVβ3 integrin antiserum was
基金the Special Funds for the State Key Basic Research Project (Grant No. G1999055903)the National Climbing Project of China (Grant No. 970211019-3) the Hundred-Scientist-Program of the Chinese Academy of Sciences.
文摘Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays a critical role in angiogenesis. Recent reports indicated that VEGF was closely involved in embryo implantation and embryonic vasculogenesis. However, very little information is available about the detailed expression and function of VEGF at implantation 'window'. In this work, VEGFs were primarily present on uterine epithelial cell monolayer and blasto-cysts including the outgrew trophoblasts at implantation window. VEGF antibodies decreased the number of mice embryos implanted and the percentage of blastocysts with attachment and outgrowth in a co-culture model in a dose-dependant manner. These findings demonstrate that VEGF is one of the essential cytokines for embryo implantation in mouse. VEGF may act as a local mediator to regulate the maternal-fetal interaction, and facilitate blastocyst implantation.
基金The authors apologize for the omission of additional applications of CRISPR/Cas9 or citations due to space limitations.This work was supported by Grant R01 AI087645(to H.H.)from the National Institutes of Health(NIH)/National Institute of Allergy and Infectious Diseases(NIAID)Grants ES017761,AG044768,AG013319,and AG044271(to A.L.F.)from the NIH as well as funds from the South Texas VA Healthcare System(ALF).
文摘CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function.More recently,this technology has been increasingly applied to the study or treatment of human diseases,including Barth syndrome effects on the heart,Duchenne muscular dystrophy,hemophilia,b-Thalassemia,and cystic fibrosis.CRISPR/Cas9(CRISPR-associated protein 9)genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo.In addition to genetic diseases,CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5,the programmed death 1 gene,or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome(AIDS)or promoting anti-tumor immunotherapy.Furthermore,this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials,including molecules,cells or organs,on a large scale.Finally,CRISPR/Cas9 has been teamed with induced pluripotent stem(iPS)cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation.This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.