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...

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Veröffentlicht in:Biochemical and biophysical research communications 2010-01, Vol.391 (1), p.329-334
Hauptverfasser: Seifinejad, Ali, Taei, Adeleh, Totonchi, Mehdi, Vazirinasab, Hamed, Hassani, Seideh Nafiseh, Aghdami, Nasser, Shahbazi, Ebrahim, Yazdi, Reza Salman, Salekdeh, Ghasem Hosseini, Baharvand, Hossein
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container_title Biochemical and biophysical research communications
container_volume 391
creator Seifinejad, Ali
Taei, Adeleh
Totonchi, Mehdi
Vazirinasab, Hamed
Hassani, Seideh Nafiseh
Aghdami, Nasser
Shahbazi, Ebrahim
Yazdi, Reza Salman
Salekdeh, Ghasem Hosseini
Baharvand, Hossein
description 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, α-globulin, and γ-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.
doi_str_mv 10.1016/j.bbrc.2009.11.058
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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, α-globulin, and γ-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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19912985</pmid><doi>10.1016/j.bbrc.2009.11.058</doi><tpages>6</tpages></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
ABO Blood-Group System
Amino Acid Sequence
ANTIGENS
Base Sequence
BLOOD CELLS
Blood Donors
Blood group systems
BLOOD GROUPS
Bombay phenotype
Cell Line
DNA
Erythrocytes - cytology
FIBROBLASTS
Fibroblasts - cytology
Fibroblasts - metabolism
Fucosyltransferases - genetics
FUT1 and FUT2 genes
Galactoside 2-alpha-L-fucosyltransferase
Gene Expression
GENES
GLOBULINS
Hematopoiesis
Humans
IN VITRO
Induced pluripotent stem cells
KARYOTYPE
Kruppel-Like Factor 4
METHYLATION
Mutation, Missense
MUTATIONS
PHENOTYPE
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
STEM CELLS
THERAPY
TRANSCRIPTION FACTORS
Transcription Factors - genetics
title Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards “universal-donor” red blood cells
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