文献类型：期刊文献

英文题名：Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche

作者：Hao, Xiaoxin[1];Gu, Hao[1];Chen, Chiqi[1];Huang, Dan[1];Zhao, Yuzheng[2];Xie, Li[1];Zou, Yejun[2];Shu, Hui Sophie[3];Zhang, Yaping[1];He, Xiaoxiao[1];Lai, Xiaoyun[1];Zhang, Xiaocui[1];Zhou, Bo O.[3];Zhang, Cheng Cheng[4];Chen, Guo-Qiang[1];Yu, Zhuo[1];Yang, Yi[2,6];Zheng, Junke[1,5]

机构：[1]Shanghai Jiao Tong Univ, Dept Pathophysiol, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ,Sch Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China;[4]UT Southwestern Med Ctr, Dept Physiol, Dallas, TX 75390 USA;[5]Shanghai Jiao Tong Univ, Shanghai Key Lab Reprod Med, Sch Med, Shanghai 200025, Peoples R China;[6]Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Inst Neurosci, Shanghai 200031, Peoples R China

年份：2019

卷号：29

期号：4

起止页码：950

外文期刊名：CELL METABOLISM

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000463015800016)】；

基金：This work was supported by grants from National Natural Science Foundation of China (81570093, 81422001, 81370654, 31722033, 91649123, and 31671484), the innovative group of NSFC (81721004, G.-Q.C.), National Basic Research Program of China (973 Program, 2014CB965000; 2015CB910403, 2017YFA050400, 2017YFC0906900), the 1,000-Youth Elite Program, Natural Science Foundation of Shanghai (17ZR1415500), National Postdoctoral Program for Innovative Talents (BX201700157), and the Shanghai Science and Technology Commission (18JC1411900).

语种：英文

摘要：The metabolic properties of leukemia-initiating cells (LICs) in distinct bone marrow niches and their relationships to cell-fate determinations remain largely unknown. Using a metabolic imaging system with a highly responsive genetically encoded metabolic sensor, SoNar, we reveal that SoNar-high cells are more glycolytic, enriched for higher LIC frequency, and develop leukemia much faster than SoNar-low counterparts in an MLL-AF9-induced murine acute myeloid leukemia model. SoNar-high cells mainly home to and locate in the hypoxic endosteal niche and maintain their activities through efficient symmetric division. SoNar can indicate the dynamics of metabolic changes of LICs in the endosteal niche. SoNar-high human leukemia cells or primary samples have enhanced clonogenic capacities in vitro or leukemogenesis in vivo. PDK2 fine-tunes glycolysis, homing, and symmetric division of LICs. These findings provide a unique angle for the study of metabolisms in stem cells, and may lead to development of novel strategies for cancer treatment.