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Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures
Mark H. Chin1,Mike J. Mason1,8,Wei Xie1,Stefano Volinia10,Mike Singer11,Cory Peterson3,Gayane Ambartsumyan2,Otaren Aimiuwu2,Laura Richter2,Jin Zhang4,Ivan Khvorostov4,Vanessa Ott11,Michael Grunstein1,Neta Lavon9,Nissim Benvenisty9,Carlo M. Croce10,Amander T. Clark2,5,6,7,Tim Baxter11,April D. Pyle3,5,6,7,Mike A. Teitell4,5,6,7,Matteo Pelegrini2,6,Kathrin Plath1,5,6,7,,andWilliam E. Lowry2,5,6,7,,
1 Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
2 Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
3 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
4 Departments of Pathology and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
5 Broad Stem Cell Center, University of California, Los Angeles, CA 90095, USA
6 Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
7 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA
8 Department of Statistics, University of California, Los Angeles, CA 90095, USA
9 Department of Genetics, Hebrew University, Jerusalem 91904, Israel
10 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
11 Roche NimbleGen, Inc., Madison, WI 53719, USA
Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.
