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

Xiaoxin Hao, Hao Gu, Chiqi Chen, Dan Huang, Yuzheng Zhao, Li Xie, Yejun Zou, Hui Sophie Shu, Yaping Zhang, Xiaoxiao He, Xiaoyun Lai, Xiaocui Zhang, Bo O. Zhou, Cheng Cheng Zhang, Guo Qiang Chen, Zhuo Yu, Yi Yang, Junke Zheng

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)950-965.e6
JournalCell Metabolism
Volume29
Issue number4
DOIs
StatePublished - Apr 2 2019

Keywords

  • PDK2
  • SoNar
  • endosteal niche
  • homing
  • leukemia-initiating cells
  • metabolic imaging
  • symmetric division

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche'. Together they form a unique fingerprint.

  • Cite this

    Hao, X., Gu, H., Chen, C., Huang, D., Zhao, Y., Xie, L., Zou, Y., Shu, H. S., Zhang, Y., He, X., Lai, X., Zhang, X., Zhou, B. O., Zhang, C. C., Chen, G. Q., Yu, Z., Yang, Y., & Zheng, J. (2019). Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche. Cell Metabolism, 29(4), 950-965.e6. https://doi.org/10.1016/j.cmet.2018.11.013