Single-Cell Mass Spectrometry Studies of Secondary Drug Resistance of Tumor Cells DOI

Guizhen Zhu,

Wenmei Zhang, Yaoyao Zhao

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Patients with epidermal growth factor receptor mutant nonsmall cell lung cancer (NSCLC) often fail to treat gefitinib because of secondary drug resistance. The development tumor resistance is closely related variations in metabolism. Single-cell metabolomics analysis can provide unique information about Herein, we constructed a platform study the cells based on single-cell (sSRTC-scM). A gefitinib-resistant NSCLC line (PC9GR) was by increasing dose step step. metabolic profiles parental PC9 and PC9GR different levels were detected intact living-cell electrolaunching ionization mass spectrometry at level. data analyzed statistical methods such as t-SNE, variance, volcano plot, heat map, pathway analysis. Using this platform, found that fingerprints evaluate degrees. continue be altered increase We revealed 19 markers variance clarified glycerophospholipid changed significantly. In addition, levels, heterogeneity metabolism became greater number weak gradually decreased. This phenomenon utilized illustrate degrees cells. provides diagnostic for evaluating tumors gives new insight into overcoming tumors.

Language: Английский

Recent progress in mass spectrometry for single-cell metabolomics DOI
Xingyu Pan, Huan Yao, Sichun Zhang

et al.

Current Opinion in Chemical Biology, Journal Year: 2022, Volume and Issue: 71, P. 102226 - 102226

Published: Nov. 5, 2022

Language: Английский

Citations

7

Organic Mass Cytometry Discriminating Cycle Stages of Single Cells with Small Molecular Indicators DOI
Shuting Xu, Cheng Yang, Xiu‐Ping Yan

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(4), P. 2312 - 2320

Published: Jan. 18, 2023

Cell cycle is a significant factor toward cellular heterogeneity, so cell discrimination precise measurement on the top of single-cell analysis. Single-cell analysis based organic mass spectrometry has received great attention for its unique ability to profile metabolome, but influence metabolome heterogeneity been overlooked until now due lack compatible method. Here, we report robust protocol combination three small molecular indicators, consisting two labels (Hoechst and docetaxel) one endogenous compound [phosphocholine (34:1)], discriminate single cells at different stages in real time by cytometry. More than 6000 HeLa were acquired an improved cytometry system build differentiation model. The model successfully discriminated cells, SCC7, Hep G2 G0/G1, S, G2/M with larger 85% sensitivity 89% specificity. Along discrimination, obvious amino acids, nucleotides, energy metabolic intermediates, phospholipids was observed among this protocol, further demonstrating necessity research potential more compounds discrimination.

Language: Английский

Citations

3

“Iridium Signature” Mass Spectrometric Probes: New Tools Integrated in a Liquid Chromatography–Mass Spectrometry Workflow for Routine Profiling of Nitric Oxide and Metabolic Fingerprints in Cells DOI

Yong-Cheng Dai,

Jing Zhou, Chudong Wei

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(23), P. 8990 - 8997

Published: June 1, 2023

Nitric oxide (NO) is a highly reactive signaling molecule involved in diverse biological processes. Simultaneous profiling of NO and associated metabolic fingerprints single assay allows more accurate assessments cell states offers the possibility to better understand its exact roles. Herein, multiplexing LC–MS workflow was established for simultaneous detection intracellular various metabolites based on novel "iridium signature" mass spectrometric probe (Ir-MSP841). This Ir-MSP841 can convert liable stable permanently charged triazole product (Ir-TP852), enabling direct MS NO. 191/193Ir-signature probe-based approach endowed with overwhelming advantages interference-free, high quantitative accuracy, great sensitivity (limit down 0.14 nM). It also reveals good linearity over wide concentration range 12.5–500 nM has been successfully employed exploring release behaviors three representative donors cells. Meanwhile, results reveal that varying concentrations distinct effects cellular metabolites. study provides robust, sensitive, versatile method numerous run expands applications biomedical research.

Language: Английский

Citations

3

In Situ Spatial Analysis of Metabolic Heterogeneity in Single Living Tumor Spheroids Using Nanocapillary-Based Electrospray Ionization Mass Spectroscopy DOI
Dandan Xia, Rong Jin, Rongrong Pan

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(27), P. 10221 - 10230

Published: June 26, 2023

Spatial metabolomic analysis of individual tumor spheroids can help investigate metabolic rearrangements in different cellular regions a spheroid. In this work, nanocapillary-based electrospray ionization mass spectroscopy (ESI-MS) method is established that could realize the spatial sampling components single living spheroid and subsequent MS for study. During penetration nanocapillary into sampling, "wound surface" at outer layer takes only 0.1% whole area maximally maintains activity inside analysis. Using ESI-MS analysis, activities inner (upper lower) layers are revealed, giving full investigation heterogeneity one first time. addition, between two-dimensional (2D)-cultured cells show obvious differences, which suggests more frequent cell-cell cell-extracellular environment interactions during culture This observation not establishes powerful tool situ but also provides molecular information to elucidate three-dimensional (3D)-cultured cell model.

Language: Английский

Citations

2

Single-Cell Mass Spectrometry Studies of Secondary Drug Resistance of Tumor Cells DOI

Guizhen Zhu,

Wenmei Zhang, Yaoyao Zhao

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Patients with epidermal growth factor receptor mutant nonsmall cell lung cancer (NSCLC) often fail to treat gefitinib because of secondary drug resistance. The development tumor resistance is closely related variations in metabolism. Single-cell metabolomics analysis can provide unique information about Herein, we constructed a platform study the cells based on single-cell (sSRTC-scM). A gefitinib-resistant NSCLC line (PC9GR) was by increasing dose step step. metabolic profiles parental PC9 and PC9GR different levels were detected intact living-cell electrolaunching ionization mass spectrometry at level. data analyzed statistical methods such as t-SNE, variance, volcano plot, heat map, pathway analysis. Using this platform, found that fingerprints evaluate degrees. continue be altered increase We revealed 19 markers variance clarified glycerophospholipid changed significantly. In addition, levels, heterogeneity metabolism became greater number weak gradually decreased. This phenomenon utilized illustrate degrees cells. provides diagnostic for evaluating tumors gives new insight into overcoming tumors.

Language: Английский

Citations

0