Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Aug 1

PMID 35912231

Authors

Fengli Zuo

Jing Yu

Xiujing He

Affiliations

Soon will be listed here.

Abstract

Aberrant metabolism contributes to tumor initiation, progression, metastasis, and drug resistance. Metabolic dysregulation has emerged as a hallmark of several hematologic malignancies. Decoding the molecular mechanism underlying metabolic rewiring in hematological malignancies would provide promising avenues for novel therapeutic interventions. Single-cell metabolic analysis can directly offer a meaningful readout of the cellular phenotype, allowing us to comprehensively dissect cellular states and access biological information unobtainable from bulk analysis. In this review, we first highlight the unique metabolic properties of hematologic malignancies and underscore potential metabolic vulnerabilities. We then emphasize the emerging single-cell metabolomics techniques, aiming to provide a guide to interrogating metabolism at single-cell resolution. Furthermore, we summarize recent studies demonstrating the power of single-cell metabolomics to uncover the roles of metabolic rewiring in tumor biology, cellular heterogeneity, immunometabolism, and therapeutic resistance. Meanwhile, we describe a practical view of the potential applications of single-cell metabolomics in hematopoiesis and hematological malignancies. Finally, we present the challenges and perspectives of single-cell metabolomics development.

Citing Articles

Insights into Metabolic Reprogramming in Tumor Evolution and Therapy.

Chiu C, Guerrero J, Regalado R, Zhou J, Zamora M, Notarte K Cancers (Basel). 2024; 16(20).

PMID: 39456607 PMC: 11506062. DOI: 10.3390/cancers16203513.

Metabolomic profiling of childhood medulloblastoma: contributions and relevance to diagnosis and molecular subtyping.

Huang R, Lu X, Sun X, Wu H J Cancer Res Clin Oncol. 2024; 150(10):471.

PMID: 39441459 PMC: 11499513. DOI: 10.1007/s00432-024-05990-1.

Glutamine and leukemia research: progress and clinical prospects.

Wang Z, Liu M, Yang Q Discov Oncol. 2024; 15(1):391.

PMID: 39215845 PMC: 11365919. DOI: 10.1007/s12672-024-01245-0.

Unveiling novel insights in acute myeloid leukemia through single-cell RNA sequencing.

Zhou J, Chng W Front Oncol. 2024; 14:1365330.

PMID: 38711849 PMC: 11070491. DOI: 10.3389/fonc.2024.1365330.

To metabolomics and beyond: a technological portfolio to investigate cancer metabolism.

Danzi F, Pacchiana R, Mafficini A, Scupoli M, Scarpa A, Donadelli M Signal Transduct Target Ther. 2023; 8(1):137.

PMID: 36949046 PMC: 10033890. DOI: 10.1038/s41392-023-01380-0.

References

Duenas M, Essner J, Lee Y . 3D MALDI Mass Spectrometry Imaging of a Single Cell: Spatial Mapping of Lipids in the Embryonic Development of Zebrafish. Sci Rep. 2017; 7(1):14946. PMC: 5668422. DOI: 10.1038/s41598-017-14949-x. View

Arguello R, Combes A, Char R, Gigan J, Baaziz A, Bousiquot E . SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution. Cell Metab. 2020; 32(6):1063-1075.e7. PMC: 8407169. DOI: 10.1016/j.cmet.2020.11.007. View

Vangapandu H, Alston B, Morse J, Ayres M, Wierda W, Keating M . Biological and metabolic effects of IACS-010759, an OxPhos inhibitor, on chronic lymphocytic leukemia cells. Oncotarget. 2018; 9(38):24980-24991. PMC: 5982765. DOI: 10.18632/oncotarget.25166. View

Gregory M, Nemkov T, Park H, Zaberezhnyy V, Gehrke S, Adane B . Targeting Glutamine Metabolism and Redox State for Leukemia Therapy. Clin Cancer Res. 2019; 25(13):4079-4090. PMC: 6642698. DOI: 10.1158/1078-0432.CCR-18-3223. View

Goldberg I . Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res. 1996; 37(4):693-707. View

Masaki A, Ishida T, Maeda Y, Ito A, Suzuki S, Narita T . Clinical significance of tryptophan catabolism in Hodgkin lymphoma. Cancer Sci. 2017; 109(1):74-83. PMC: 5765298. DOI: 10.1111/cas.13432. View

Zaslona Z, ONeill L . Cytokine-like Roles for Metabolites in Immunity. Mol Cell. 2020; 78(5):814-823. DOI: 10.1016/j.molcel.2020.04.002. View

Martinez-Outschoorn U, Lin Z, Trimmer C, Flomenberg N, Wang C, Pavlides S . Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors. Cell Cycle. 2011; 10(15):2504-20. PMC: 3180189. DOI: 10.4161/cc.10.15.16585. View

Shime H, Yabu M, Akazawa T, Kodama K, Matsumoto M, Seya T . Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol. 2008; 180(11):7175-83. DOI: 10.4049/jimmunol.180.11.7175. View

10.

Levine L, Hiam-Galvez K, Marquez D, Tenvooren I, Madden M, Contreras D . Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8 T cells during the primary immune response. Immunity. 2021; 54(4):829-844.e5. PMC: 8046726. DOI: 10.1016/j.immuni.2021.02.018. View

11.

Song K, Li M, Xu X, Xuan L, Huang G, Liu Q . Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia. Oncol Lett. 2016; 12(1):334-342. PMC: 4906727. DOI: 10.3892/ol.2016.4600. View

12.

Wang Y, Israelsen W, Lee D, Yu V, Jeanson N, Clish C . Cell-state-specific metabolic dependency in hematopoiesis and leukemogenesis. Cell. 2014; 158(6):1309-1323. PMC: 4197056. DOI: 10.1016/j.cell.2014.07.048. View

13.

Willems L, Jacque N, Jacquel A, Neveux N, Trovati Maciel T, Lambert M . Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood. 2013; 122(20):3521-32. PMC: 3829119. DOI: 10.1182/blood-2013-03-493163. View

14.

Bolzoni M, Chiu M, Accardi F, Vescovini R, Airoldi I, Storti P . Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target. Blood. 2016; 128(5):667-79. DOI: 10.1182/blood-2016-01-690743. View

15.

Cong Y, Liang Y, Motamedchaboki K, Huguet R, Truong T, Zhao R . Improved Single-Cell Proteome Coverage Using Narrow-Bore Packed NanoLC Columns and Ultrasensitive Mass Spectrometry. Anal Chem. 2020; 92(3):2665-2671. PMC: 7550239. DOI: 10.1021/acs.analchem.9b04631. View

16.

Carew J, Nawrocki S, Xu R, Dunner K, McConkey D, Wierda W . Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on sensitivity to fludarabine. Leukemia. 2004; 18(12):1934-40. DOI: 10.1038/sj.leu.2403545. View

17.

Campillo-Marcos I, Alvarez-Errico D, Alandes R, Mereu E, Esteller M . Single-cell technologies and analyses in hematopoiesis and hematological malignancies. Exp Hematol. 2021; 98:1-13. DOI: 10.1016/j.exphem.2021.05.001. View

18.

Fujiwara S, Wada N, Kawano Y, Okuno Y, Kikukawa Y, Endo S . Lactate, a putative survival factor for myeloma cells, is incorporated by myeloma cells through monocarboxylate transporters 1. Exp Hematol Oncol. 2015; 4:12. PMC: 4407384. DOI: 10.1186/s40164-015-0008-z. View

19.

Passarelli M, Ewing A . Single-cell imaging mass spectrometry. Curr Opin Chem Biol. 2013; 17(5):854-9. PMC: 3823831. DOI: 10.1016/j.cbpa.2013.07.017. View

20.

Liu Z, Portero E, Jian Y, Zhao Y, Onjiko R, Zeng C . Trace, Machine Learning of Signal Images for Trace-Sensitive Mass Spectrometry: A Case Study from Single-Cell Metabolomics. Anal Chem. 2019; 91(9):5768-5776. PMC: 6709531. DOI: 10.1021/acs.analchem.8b05985. View