Open AccessHematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells
Author(s) -
Choi KyungDal,
Yu Junying,
SmugaOtto Kim,
Salvagiotto Giorgia,
Rehrauer William,
Vodyanik Maxim,
Thomson James,
Slukvin Igor
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0922
Subject(s) - biology , induced pluripotent stem cell , sox2 , reprogramming , cd34 , microbiology and biotechnology , embryonic stem cell , haematopoiesis , stem cell , homeobox protein nanog , kosr , endothelial stem cell , klf4 , cellular differentiation , embryoid body , immunology , genetics , in vitro , cell , gene
Induced pluripotent stem cells (iPSCs) provide an unprecedented opportunity for modeling of human diseases in vitro, as well as for developing novel approaches for regenerative therapy based on immunologically compatible cells. In this study, we employed an OP9 differentiation system to characterize the hematopoietic and endothelial differentiation potential of seven human iPSC lines obtained from human fetal, neonatal, and adult fibroblasts through reprogramming with POU5F1, SOX2, NANOG, and LIN28 and compared it with the differentiation potential of five human embryonic stem cell lines (hESC, H1, H7, H9, H13, and H14). Similar to hESCs, all iPSCs generated CD34 + CD43 + hematopoietic progenitors and CD31 + CD43 − endothelial cells in coculture with OP9. When cultured in semisolid media in the presence of hematopoietic growth factors, iPSC‐derived primitive blood cells formed all types of hematopoietic colonies, including GEMM colony‐forming cells. Human induced pluripotent cells (hiPSCs)‐derived CD43 + cells could be separated into the following phenotypically defined subsets of primitive hematopoietic cells: CD43 + CD235a + CD41a ± (erythro‐megakaryopoietic), lin − CD34 + CD43 + CD45 − (multipotent), and lin − CD34 + CD43 + CD45 + (myeloid‐skewed) cells. Although we observed some variations in the efficiency of hematopoietic differentiation between different hiPSCs, the pattern of differentiation was very similar in all seven tested lines obtained through reprogramming of human fetal, neonatal, or adult fibroblasts with three or four genes. Although several issues remain to be resolved before iPSC‐derived blood cells can be administered to humans for therapeutic purposes, patient‐specific iPSCs can already be used for characterization of mechanisms of blood diseases and for identification of molecules that can correct affected genetic networks. S TEM C ELLS 2009;27:559–567