Cell research: Xie Xin group of Shanghai Pharmaceutical Research Institute first used small molecular compounds to achieve in vivo myocardial cell transdifferentiation

The study of somatic reprogramming and transdifferentiation provides new ideas for cell replacement therapy and drug screening in vitro The early reprogramming of somatic cells needs to be realized by the combination of virus carrying related transcription factors Small molecular compounds have been paid more attention in the study of somatic reprogramming and transdifferentiation because of their easy control of dose and time and good prospect of drug preparation At present, small molecule combination can successfully induce many kinds of somatic cells into induced pluripotent stem cells (iPSCs), neural precursor cells, neurons, endodermal precursor cells and cardiomyocytes in vitro However, it is not clear whether small molecular combinations can induce in situ reprogramming of somatic cells in vivo Xie Xin research group of Shanghai Institute of drugs has been devoted to the induction of reprogramming and transdifferentiation of somatic cells by small molecular compounds In 2015, it was reported that the combination of small molecular compounds including BrdU can realize the full chemical induction of iPSCs in vitro; in the same year, the combination of 3-7 small molecular compounds successfully achieved the transdifferentiation of mouse embryonic fibroblasts into cardiomyocytes in vitro These chemically induced cardiac like cells (CICMs) can automatically contract rhythmically, express cardiac specific genes, and have similar electrophysiological characteristics    Based on the hypothesis that the microenvironment of the heart in vivo may contribute to the production and survival of CICM, recently, Xie Xin's team boldly gave the small molecule combination crfvptm (C: chir99021; R: repsox; F: forskolin; V: VPA; P: parnate; t: ttnpb; m: rolipram) which can induce CICM to produce to mice in vitro, and found that the small molecule combination can transfer the heart through pedigree tracking experiment The fibroblasts in the viscera were induced into CICM, and the transdifferentiation began only one week after administration After six weeks of administration, CICM appeared close to the adjacent cardiomyocytes in morphology and expression of various cardiac related markers What's more, this small molecule combination can effectively inhibit the fibrosis of the heart and promote the recovery of heart function in mice with myocardial infarction At present, the efficiency of differentiation of cardiomyocytes induced by small molecular compounds remains to be improved, but this study conceptually confirmed that small molecular drugs can induce in situ reprogramming and functional repair of somatic cells in vivo, which laid a foundation for further research The research results were recently published online in cell research (DOI: 10.1038/s41422-018-0036-4) The research was completed under the guidance of researcher Xie Xin, and the first author of the paper was Huang Chenwen, a doctoral student of Tongji University Xie Xin is mainly engaged in the research of new drug discovery and mechanism based on GPCR, as well as the research of small molecular compounds regulating the fate of stem cells The research work was supported by the "organ reconstruction and manufacturing" pilot project of the Chinese Academy of Sciences, the major scientific research plan of the Ministry of science and technology and the National Natural Science Foundation.