title: Generation of induced pluripotent stem cells without genetic defects by small molecules.
abstract: The generation of induced pluripotent stem cells (iPSCs) often causes genetic and epigenetic defects, which may limit their clinical applications. Here, we show that reprogramming in the presence of small molecules preserved the genomic stability of iPSCs by inhibiting DNA double-strand breaks (DSBs) and activating Zscan4 gene. Surprisingly, the small molecules protected normal karyotype by facilitating repair of the DSBs that occurred during the early reprogramming process and long-term culture of iPSCs. The stemness and cell growth of iPSCs(+) were normally sustained with high expression of pluripotency genes compared that of iPSCs(-). Moreover, small molecules maintained the differentiation potential of iPSCs(+) for the three germ layers, whereas it was lost in iPSCs(-). Our results demonstrate that the defined small molecules are potent factors for generation of high quality iPSCs with preservation of genomic integrity by facilitating the reprogramming process.
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Sungbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Hang-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Sungbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Insik
authors.initials: I
authors.lastname: Hwang
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Sungbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Choi
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Sungbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Hyesun
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Pathology, College of Medicine, Korea University, Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Sungbuk-gu, Seoul 136-703, Republic of Korea. Electronic address: shong21@korea.ac.kr.
authors.forename: Sunghoi
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D011743:Pyrimidines; D013844:Thiazoles; C545214:thiazovivin; C506614:mirdametinib; D004159:Diphenylamine; D001205:Ascorbic Acid
keywords: DNA double-strand breaks; Genomic stability; Induced pluripotent stem cells; Small molecules