Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.
Recent evidence suggests human embryonic stem cell (hESC) and induced pluripotent stem (iPS) cell lines have differences in their epigenetic marks and transcriptomes, yet the impact of these differences on subsequent terminally differentiated cells is less well understood. Comparison of purified, homogeneous populations of somatic cells derived from multiple independent human iPS and ES lines will be required to address this critical question. Here, we report a differentiation protocol based on embryonic development that consistently yields large numbers of endothelial cells (ECs) derived from multiple hESCs or iPS cells. Mesoderm differentiation of embryoid bodies was maximized, and defined growth factors were used to generate KDR(+) EC progenitors. Magnetic purification of a KDR(+) progenitor subpopulation resulted in an expanding, homogeneous pool of ECs that expressed EC markers and had functional properties of ECs. Comparison of the transcriptomes revealed limited gene expression variability between multiple lines of human iPS-derived ECs or between lines of ES- and iPS-derived ECs. These results demonstrate a method to generate large numbers of pure human EC progenitors and differentiated ECs from pluripotent stem cells and suggest individual lineages derived from human iPS cells may have significantly less variance than their pluripotent founders.
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA.
Mark P
MP
White
Abdul J
AJ
Rufaihah
Lei
L
Liu
Yohannes T
YT
Ghebremariam
Kathryn N
KN
Ivey
John P
JP
Cooke
Deepak
D
Srivastava
D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020796:Receptor, Platelet-Derived Growth Factor alpha; D040301:Vascular Endothelial Growth Factor Receptor-2