title: Generation of human induced pluripotent stem cells from a Bombay individual: moving towards "universal-donor" red blood cells.
abstract: Bombay phenotype is one of the rare phenotypes in the ABO blood group system that fails to express ABH antigens on red blood cells. Nonsense or missense mutations in fucosyltransfrase1 (FUT1) and fucosyltransfrase2 (FUT2) genes are known to create this phenotype. This blood group is compatible with all other blood groups as a donor, as it does not express the H antigen on the red blood cells. In this study, we describe the establishment of human induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of a Bombay blood-type individual by the ectopic expression of established transcription factors Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of fibroblasts and iPSCs revealed a nonsense mutation 826C to T (276 Gln to Ter) in the FUT1 gene and a missense mutation 739G to A (247 Gly to Ser) in the FUT2 gene in the Bombay phenotype under study. The established iPSCs resemble human embryonic stem cells in morphology, passaging, surface and pluripotency markers, normal karyotype, gene expression, DNA methylation of critical pluripotency genes, and in-vitro differentiation. The directed differentiation of the iPSCs into hematopoietic lineage cells displayed increased expression of the hematopoietic lineage markers such as CD34, CD133, RUNX1, KDR, alpha-globulin, and gamma-globulin. Such specific stem cells provide an unprecedented opportunity to produce a universal blood group donor, in-vitro, thus enabling cellular replacement therapies, once the safety issue is resolved.
authors.affiliation: Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, PO Box 19395-4644, ACECR, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Seifinejad
authors.forename: Adeleh
authors.initials: A
authors.lastname: Taei
authors.forename: Mehdi
authors.initials: M
authors.lastname: Totonchi
authors.forename: Hamed
authors.initials: H
authors.lastname: Vazirinasab
authors.forename: Seideh Nafiseh
authors.initials: SN
authors.lastname: Hassani
authors.forename: Nasser
authors.initials: N
authors.lastname: Aghdami
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shahbazi
authors.forename: Reza Salman
authors.initials: RS
authors.lastname: Yazdi
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000017:ABO Blood-Group System; D000595:Amino Acid Sequence; D001483:Base Sequence; D001782:Blood Donors; D002460:Cell Line; D004912:Erythrocytes / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics; D015870:Gene Expression; D006410:Hematopoiesis; D006801:Humans; D000090062:Kruppel-Like Factor 4; D020125:Mutation, Missense; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D005647:Fucosyltransferases; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C000715467:KLF4 protein, human