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          重點實驗室高瀛岱研究員等在Nature Communications發表文章

            我重點實驗室高瀛岱研究員等在Nature Communications發表文章“Small-molecule inhibitors targeting INK4 protein ?p18INK4C enhance ex vivoexpansion of haematopoietic stem cells”,該文章于2015年2月18日發表,其中共同第一作者為高瀛岱、楊鵬、沈紅梅,通訊作者為程濤教授和解向群教授。


            Among cyclin-dependent kinase inhibitors that control the G1 phase in cell cycle, only p18 and p27 can negatively regulate haematopoietic stem cell (HSC) self-renewal. In this manuscript, we demonstrate that p18 protein is a more potent inhibitor of HSC self-renewal than p27 in mouse models and its deficiency promoted HSC expansion in long-term culture. Single-cell analysis indicated that deleting p18 gene favoured self-renewing division of HSC in vitro. Based on the structure of p18 protein and in-silico screening, we further identified novel smallmolecule inhibitors that can specifically block the activity of p18 protein. Our selected lead compounds were able to expand functional HSCs in a short-term culture. Thus, these putative small-molecule inhibitors for p18 protein are valuable for further dissecting the signaling pathways of stem cell self-renewal and may help develop more effective chemical agents for therapeutic expansion of HSC.


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