Sirt6通过表观遗传调控Wnt信号通路控制造血干细胞的稳态  

SIRT6 Controls Hematopoietic Stem Cell Homeostasis through Epigenetic Regulation of Wnt Signaling

作　　者：汪虎 Daojun Diao Zhencan Shi Xudong Zhu Yawei Gao Shaorong Gao Xiaoyu Liu You Wu K.Lenhard Rudolph Guanghui Liu Tangliang Li 鞠振宇[1] 

机构地区：[1]杭州师范大学衰老研究所 [2]不详

出　　处：《科学新闻》2017年第4期64-64,共1页Science News

基　　金：科技部973计划(2012CB911203);国家自然科学基金杰出青年基金(81525010);国家自然科学基金国际合作项目(81420108017);国家自然科学基金重点项目(81130074);优秀青年项目(81222003)等资助

摘　　要：Wnt信号通路对造血干细胞稳态的维持是至关重要的，但Wnt信号在造血干细胞中的表观遗传调控规律仍然是未知的。Proper regulation of Wnt signaling is critical for the maintenance of hematopoietic stem cell (HSC) homeostasis. The epigenetic regulation of Wnt signaling in HSCs remains largely unknown. Here, we report that the histone deacetylase SIRT6 regulates HSC homeostasis through the transcriptional repression of Wnt target genes. Sirt6 deletion promoted HSC proliferation through aberrant activation of Wnt signaling. SIRT6-deficient HSCs exhibited impaired self-renewal ability in serial competitive transplantation assay. Mechanistically, SIRT6 inhibits the transcription of Wnt target genes by interacting with transcription factor LEF1 and deacetylating histone 3 at lysine 56. Pharmacological inhibition of the Wnt pathway rescued the aberrant proliferation and functional defect in SIRT6-deficient HSCs. Taken together, these findings disclose a new link between SIRT6 and Wnt signaling in the regulation of adult stem cell homeostasis and self-renewal capacity.

关 键 词：造血干细胞 信号 通路 遗传 

分 类 号：Q813[生物学—生物工程]