Abstract
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold tremendous clinical potential because of their ability to self-renew, and to differentiate into all cell types of the body. This unique capacity of ESCs and iPSCs to form all cell lineages is termed pluripotency. While ESCs and iPSCs are pluripotent and remarkably similar in appearance, whether iPSCs truly resemble ESCs at the molecular level is still being debated. Further research is therefore needed to resolve this issue before iPSCs may be safely applied in humans for cell therapy or regenerative medicine. Nevertheless, the use of iPSCs as an in vitro human genetic disease model has been useful in studying the molecular pathology of complex genetic diseases, as well as facilitating genetic or drug screens. Here, we review recent progress in transcriptomic approaches in the study of ESCs and iPSCs, and discuss how deregulation of these pathways may be involved in the development of disease. Finally, we address the importance of these advances for developing new therapeutics, and the future challenges facing the clinical application of ESCs and iPSCs.
Highlights
Embryonic stem cells (ESCs) and induced pluripotent stem cells hold tremendous clinical potential because of their ability to self-renew, and to di erentiate into all cell types of the body
Studies on ESCs led to the discovery of the core pluripotency factors Oct4, Klf4 and c-Myc (Sox2) and Nanog [1], and, increasingly, the use of genome-level screening assays has revealed new insights by uncovering additional transcription factors, transcriptional cofactors and chromatin remodeling complexes involved in the maintenance of pluripotency [1]. e study of ESC transcriptional regulation is useful in the understanding of human diseases
The use of human ESCs in clinical applications has been slow because of ethical, immunological and tumorigenicity concerns [3]. ese ethical and immunogenicity issues were seemingly overcome by the creation of induced pluripotent stem cells, whereby exogenous expression of Oct4, Sox2, Klf4 and c-Myc in differentiated cells could revert them to pluripotency [4]
Summary
BS-seq, bisulfite sequencing; ChIA-PET, chromatin interaction analysis with paired-end tag sequencing; ChIP-chip, chromatin immunoprecipitation on chip; ChIP-PET, chromatin immunoprecipitation with paired-end tag sequencing; ChIP-seq, chromatin immunoprecipitation and sequencing; DIPseq, DNA immunoprecipitation and sequencing; MethylC-seq, methylcytosine sequencing; NGS, next-generation sequencing; RIP, RNA-binding protein immunoprecipitation; RIP-seq, RNA-binding protein immunoprecipitation and sequencing; RNA-seq, RNA sequencing; 3C, chromosome conformation capture. It was previously reported that cancer cells possess an ESC-like transcriptional program, suggest ing that ESC-associated genes may contribute to tumor formation [72] This expression signature was shown to be a result of c-Myc, rather than from the core pluripotency factors (Table 3) [9]. As c-Myc somatic copynumber duplications are the most frequent in cancer [73], the finding that c-Myc releases RNA polymerase II from transcriptional pause [28] offers new unders tanding into the transcriptional regulatory role of c-Myc in ESCs and cancer cells Another pluripotency-associated factor, Lin, which suppresses the maturation of pro-differen tiation let-7 miRNA, is highly expressed in poorly differentiated and low prognosis tumors [74]. It would be necessary to experimentally verify if iPSC-derived differentiated cells are immunogenic in syngeneic hosts
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
