title: Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells.
abstract: C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Δ32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndrome (AIDS). However, Δ32 donors are scarce, heterologous bone marrow transplantation is not exempt of risks, and genetic engineering of autologous hHSCs is not trivial. Here, we have disrupted the CCR5 locus of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) using specific zinc finger nucleases (ZFNs) combined with homologous recombination. The modified hESCs and hiPSCs retained pluripotent characteristics and could be differentiated in vitro into CD34(+) cells that formed all types of hematopoietic colonies. Our results suggest the potential of using patient-specific hHSCs derived from ZFN-modified hiPSCs for treating AIDS.
authors: Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Chinese Academy of Sciences , Guangzhou, China.
authors: Yongchao
authors: Y
authors: Yao
authors: Bayaer
authors: B
authors: Nashun
authors: Tiancheng
authors: T
authors: Zhou
authors: Li
authors: L
authors: Qin
authors: Limei
authors: L
authors: Qin
authors: Siting
authors: S
authors: Zhao
authors: Jianyong
authors: J
authors: Xu
authors: Miguel A
authors: MA
authors: Esteban
authors: Xiaoping
authors: X
authors: Chen
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D005818:Genetic Engineering; D005822:Genetic Vectors; D059765:Homologous Recombination; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D016335:Zinc Fingers
chemical_list: D018952:Antigens, CD34; D019713:Receptors, CCR5; D003851:Deoxyribonucleases