Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. 2009

Kyung-Dal Choi, and Junying Yu, and Kim Smuga-Otto, and Giorgia Salvagiotto, and William Rehrauer, and Maxim Vodyanik, and James Thomson, and Igor Slukvin
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, 53715, USA.

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.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006413 Hematopoietic System The blood-making organs and tissues, principally the bone marrow and lymph nodes. Hematopoietic Systems,System, Hematopoietic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D051917 Leukosialin A sialic acid-rich protein and an integral cell membrane mucin. It plays an important role in activation of T-LYMPHOCYTES. Antigens, CD43,CD43 Antigens,CD43 Antigen,Leukocyte Sialoglycoprotein,Sialophorin,Antigen, CD43,Sialoglycoprotein, Leukocyte
D053595 Embryonic Stem Cells Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells. Stem Cells, Embryonic,Cell, Embryonic Stem,Cells, Embryonic Stem,Embryonic Stem Cell,Stem Cell, Embryonic
D018952 Antigens, CD34 Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow. CD34 Antigens,CD34 Antigen,Antigen, CD34
D039904 Pluripotent Stem Cells Cells that can give rise to cells of the three different GERM LAYERS. Stem Cells, Pluripotent,Pluripotent Stem Cell,Stem Cell, Pluripotent

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