Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders.
Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.
Stem Cell Program, Institute for Cell Engineering, and Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhaohui
Z
Ye
Huichun
H
Zhan
Prashant
P
Mali
Sarah
S
Dowey
Donna M
DM
Williams
Yoon-Young
YY
Jang
Chi V
CV
Dang
Jerry L
JL
Spivak
Alison R
AR
Moliterno
Linzhao
L
Cheng
D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D004920:Erythropoiesis; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018952:Antigens, CD34; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D017493:Leukocyte Common Antigens