title: Generating hESCs with reduced immunogenicity by disrupting TAP1 or TAPBP.
abstract: Human embryonic stem cells (hESCs) are thought to be a promising resource for cell therapy, while it has to face the major problem of graft immunological rejection. Major histocompatibility complex (MHC) class I expressed on the cell surface is the major cause of graft rejection. Transporter associated with antigen presentation 1 (TAP1) and TAP-associated glycoprotein (TAPBP) play important roles in regulating MHC class I expression. In this study, we generated TAP1- and TAPBP-deficient hESC lines, respectively, using transcription activator-like effector nucleases technique. These cells showed deficient expression of MHC class I on the cell surface and reduced immunogenicity compared with wild types, but maintained normal pluripotency, karyotypes, and differentiation ability. Thus, our findings are instrumental in developing a universal cell resource with both pluripotency and hypo-immunogenicity for transplantation therapy in the future.
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Cui
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Wang
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: c Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai , P.R. China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Rao
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Haide
authors.initials: H
authors.lastname: Chen
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Li
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: d Xiangtan Center Hospital , Hunan , P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: e Wuxi Medical School , Jiangnan University , Wuxi , P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cui
authors.affiliation: a College of Animal Science, Stem Cell and Developmental Biology Research Center , Zhejiang University , Hangzhou , P.R. China.|b School of Medicine , Zhejiang University , Hangzhou , P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D005818:Genetic Engineering; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology*; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; C073119:TAP1 protein, human; C107762:tapasin
keywords: TAP-associated glycoprotein (TAPBP); immune rejection; major histocompatibility complex (MHC) class I; transcription activator-like effector nucleases (TALEN); transporter associated with antigen presentation 1 (TAP1)