Generation of human induced pluripotent stem cells from a Bombay individual: moving towards "universal-donor" red blood cells.
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.
Seifinejad
Ali
A
Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, PO Box 19395-4644, ACECR, Tehran, Iran.
Taei
Adeleh
A
Totonchi
Mehdi
M
Vazirinasab
Hamed
H
Hassani
Seideh Nafiseh
SN
Aghdami
Nasser
N
Shahbazi
Ebrahim
E
Yazdi
Reza Salman
RS
Salekdeh
Ghasem Hosseini
GH
Baharvand
Hossein
H
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
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