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-5hydroxy-indirubin-3oxime (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.