@article{46a4eea2a0b142afa7a81b1fdd9d872e,
title = "Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche",
abstract = "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. Hao et al. reveal that a genetically encoded metabolic sensor, SoNar, precisely monitors the metabolic status of leukemia-initiating cells (LICs) both in vitro and in vivo. LICs prefer homing to endosteal niches and symmetric divisions to maintain their leukemogenic activities. PDK2 fine-tunes the glycolysis and cell-fate determinations of LICs.",
keywords = "PDK2, SoNar, endosteal niche, homing, leukemia-initiating cells, metabolic imaging, symmetric division",
author = "Xiaoxin Hao and Hao Gu and Chiqi Chen and Dan Huang and Yuzheng Zhao and Li Xie and Yejun Zou and Shu, {Hui Sophie} and Yaping Zhang and Xiaoxiao He and Xiaoyun Lai and Xiaocui Zhang and Zhou, {Bo O.} and Zhang, {Cheng Cheng} and Chen, {Guo Qiang} and Zhuo Yu and Yi Yang and Junke Zheng",
note = "Funding Information: 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 ). Funding Information: 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). X. Hao, H.G. C.C. Z.Y. Y.Y. and J.Z. designed the experiments, performed the experiments, analyzed data, and wrote the paper; D.H. Y. Zhao, L.X. Y. Zou, H.S.S. Y. Zhang, X. He, X.L. and X.Z. performed the experiments.; B.O.Z. C.C.Z. and G.-Q.C. provided reagents and helped with the experiments. The authors declare no competing interests.",
year = "2019",
month = apr,
day = "2",
doi = "10.1016/j.cmet.2018.11.013",
language = "English (US)",
volume = "29",
pages = "950--965.e6",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}