机构：[1]State Key Laboratory of Experimental Hematology, Beijing, China.[2]National Clinical Research Center for Blood Diseases, Tianjin, China.[3]Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.[4]Department of Hematology, the First People’s Hospital of Yunnan Province, Yunnan, China.内科片血液内科云南省第一人民医院[5]Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.[6]Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.[7]Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.[8]School of Life Sciences and Technology, Tongji University, Shanghai, China.
Applying somatic cell reprogramming strategies in cancer cell biology is a powerful approach to analyze mechanisms of malignancy and develop new therapeutics. Here, we test whether leukemia cells can be reprogrammed in vivo using the canonical reprogramming transcription factors-Oct4, Sox2, Klf4, and c-Myc (termed as OSKM). Unexpectedly, we discover that OSKM can eradicate leukemia cells and dramatically improve survival of leukemia-bearing mice. By contrast, OSKM minimally impact normal hematopoietic cells. Using ATAC-seq, we find OSKM induce chromatin accessibility near genes encoding apoptotic regulators in leukemia cells. Moreover, this selective effect also involves downregulation of H3K9me3 as an early event. Dissection of the functional effects of OSKM shows that Klf4 and Sox2 play dominant roles compared to c-Myc and Oct4 in elimination of leukemia cells. These results reveal an intriguing paradigm by which OSKM-initiated reprogramming induction can be leveraged and diverged to develop novel anti-cancer strategies.
基金：
This work was supported by grants from the Ministry of Science and
Technology of China (2016YFA0100600, 2017YFA0103400), the National Natural Science
Foundation of China (81421002, 81430004, 81922002, 81890990, 81730006,
81861148029, 81870086, 81700164, 81700166, 31522031, 31571526, 81900113). CAMS
Initiative for Innovative Medicine (2017-I2M-3-009, 2016-I2M-1-017), CAMS Fundamental
Research Funds for Central Research Institutes (2018PT31005, 2017PT31032),
SKLEH-Pilot Research Grant (Zk18-02, Zk18-05, Zk17-04) and China Postdoctoral
Science Foundation 2019M650573.
第一作者机构：[1]State Key Laboratory of Experimental Hematology, Beijing, China.[2]National Clinical Research Center for Blood Diseases, Tianjin, China.[3]Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.[4]Department of Hematology, the First People’s Hospital of Yunnan Province, Yunnan, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Experimental Hematology, Beijing, China.[2]National Clinical Research Center for Blood Diseases, Tianjin, China.[3]Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.[6]Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.[7]Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.
推荐引用方式(GB/T 7714)：
Wang Yajie,Lu Ting,Sun Guohuan,et al.Targeting of apoptosis gene loci by reprogramming factors leads to selective eradication of leukemia cells[J].NATURE COMMUNICATIONS.2019,10:doi:10.1038/s41467-019-13411-y.
APA：
Wang, Yajie,Lu, Ting,Sun, Guohuan,Zheng, Yawei,Yang, Shangda...&Cheng, Tao.(2019).Targeting of apoptosis gene loci by reprogramming factors leads to selective eradication of leukemia cells.NATURE COMMUNICATIONS,10,
MLA：
Wang, Yajie,et al."Targeting of apoptosis gene loci by reprogramming factors leads to selective eradication of leukemia cells".NATURE COMMUNICATIONS 10.(2019)
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