title: 5-Nitro-5'hydroxy-indirubin-3'oxime is a novel inducer of somatic cell transdifferentiation.
abstract: Patient-derived cell transplantation is an attractive therapy for regenerative medicine. However, this requires effective strategies to reliably differentiate patient cells into clinically useful cell types. Herein, we report the discovery that 5-nitro-5'hydroxy-indirubin-3'oxime (5'-HNIO) is a novel inducer of cell transdifferentiation. 5'-HNIO induced muscle transdifferentiation into adipogenic and osteogenic cells. 5'-HNIO was shown to inhibit aurora kinase A, which is a known cell fate regulator. 5'-HNIO produced a favorable level of transdifferentiation compared to other aurora kinase inhibitors and induced transdifferentiation across cell lineage boundaries. Significantly, 5'-HNIO treatment produced direct transdifferentiation without up-regulating potentially oncogenic induced pluripotent stem cell (iPSC) reprogramming factors. Thus, our results demonstrate that 5'-HNIO is an attractive molecular tool for cell transdifferentiation and cell fate research.
authors.affiliation: New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Da-Woon
authors.initials: DW
authors.lastname: Jung
authors.forename: Young J
authors.initials: YJ
authors.lastname: Hong
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Woong-Hee
authors.initials: WH
authors.lastname: Kim
authors.forename: Shinae
authors.initials: S
authors.lastname: Seo
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Darren R
authors.initials: DR
authors.lastname: Williams
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects*; D065150:Cellular Reprogramming / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D064096:Aurora Kinase A; C027185:indirubin
keywords: Aurora kinase; Cell transdifferentiation; Chemical biology; Indirubin; Small molecules