通过计算机模拟发现小分子物质，以有效促进干细胞向确定性内胚层分化。
In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm.
机构信息
BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada; Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.
出版信息
Stem Cell Reports. 2023 Mar 14;18(3):765-781. doi: 10.1016/j.stemcr.2023.01.008. Epub 2023 Feb 16.
Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by inclusion of this compound achieves the same differentiation efficiency with a 90% cost reduction. The presented in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.
提高人类胚胎干细胞分化方法是现代再生医学研究的一个挑战。我们采用药物再利用方法，发现了能调节原肠胚形成的小分子。其中包括已知参与内胚层分化的过程（mTOR、PI3K 和 JNK 途径）抑制剂，以及一种新的化合物，其作用机制未知，能够在培养基中没有生长因子的情况下诱导内胚层形成。通过包含该化合物来优化经典方案，可将分化效率提高到相同水平，同时成本降低 90%。所提出的候选分子选择的计算机模拟程序具有广泛的潜力，可以改进干细胞分化方案。
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