Abstract 15020: Transcriptomic and Epigenomic Resemblance of Terminally Differentiated Cells Derived From Isogenic Human iPSCs and Nuclear Transfer Derived ESCs
Human pluripotent stem cells (PSCs) hold great promise for disease modeling, drug discovery, and regenerative medicine. Currently, patient-specific PSCs can be created via two approaches: somatic cell nuclear transfer (SCNT) by enucleated oocytes and iPSC reprogramming by ectopic expression of four transcription factors. Recent studies suggest that human SCNT-derived embryonic stem cells (nt-ESCs) are more similar to in vitro fertilized embryo derived ESCs (IVF-ESCs) than iPSCs at both transcriptomic and epigenomic levels. As terminally differentiated cells (i.e., cardiomyocytes, hepatocytes, neurons, and endothelial cells) are mostly desired for clinical application of human PSCs, here we assessed the molecular and functional similarity of terminally differentiated cells derived from human isogenic iPSCs and nt-ESCs. We differentiated three types of PSCs (iPSCs, nt-ESCs, and IVF-ESCs) into beating cardiomyocytes (PSC-CMs) and functional endothelial cells (PSC-ECs), respectively. During the process of induced differentiation, human nt-ESCs displayed closer dynamic marker gene expression profiles to IVF-ESCs than iPSCs. However, terminally differentiated cells (CMs and ECs) derived from iPSCs and nt-ESCs showed comparable differentiation efficiency, lineage marker gene expression, heterogeneity, nitric oxide release and tube formation capacity. Furthermore, iPSC-CMs were clustered more closely to nt-ESC-CMs than IVF-ESC-CMs at transcriptional level revealed by RNA-seq. DNA methylome analysis by RRBS-seq indicated that iPSC-CMs and iPSC-ECs were epigenetically similar to nt-ESC-CMs and nt-ESC-ECs, respectively, but were distinguishable from IVF-ESC derivatives. Thus, for generating terminally differentiated cells, human iPSCs are comparable to their isogenic nt-ESCs with respect to transcriptomic, epigenomic, and functional features.
Author Disclosures: M. Zhao: None. H. Chen: None. Q. Liu: None. N. Sayed: None. N. Shao: None. Y. Kim: None. H. Yang: None. T. Chour: None. H. Ma: None. R. Tippner-Hedges: None. S. Mitalipov: None. M. Snyder: None. J. Wu: None.
- © 2016 by American Heart Association, Inc.