PMID- 37585522 OWN - NLM STAT- MEDLINE DCOM- 20230818 LR - 20230921 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 9 IP - 33 DP - 2023 Aug 18 TI - Profiling single cancer cell metabolism via high-content SRS imaging with chemical sparsity. PG - eadg6061 LID - 10.1126/sciadv.adg6061 [doi] LID - eadg6061 AB - Metabolic reprogramming in a subpopulation of cancer cells is a hallmark of tumor chemoresistance. However, single-cell metabolic profiling is difficult because of the lack of a method that can simultaneously detect multiple metabolites at the single-cell level. In this study, through hyperspectral stimulated Raman scattering (hSRS) imaging in the carbon-hydrogen (C-H) window and sparsity-driven hyperspectral image decomposition, we demonstrate a high-content hSRS (h(2)SRS) imaging approach that enables the simultaneous mapping of five major biomolecules, including proteins, carbohydrates, fatty acids, cholesterol, and nucleic acids at the single-cell level. h(2)SRS imaging of brain and pancreatic cancer cells under chemotherapy revealed acute and adapted chemotherapy-induced metabolic reprogramming and the unique metabolic features of chemoresistance. Our approach is expected to facilitate the discovery of therapeutic targets to combat chemoresistance. This study illustrates a high-content, label-free chemical imaging approach that measures metabolic profiles at the single-cell level and warrants further research on cellular metabolism. FAU - Tan, Yuying AU - Tan Y AUID- ORCID: 0000-0003-2536-4778 AD - Biomedical Engineering, Boston University, Boston, MA 02155, USA. FAU - Lin, Haonan AU - Lin H AUID- ORCID: 0000-0003-0437-5902 AD - Biomedical Engineering, Boston University, Boston, MA 02155, USA. FAU - Cheng, Ji-Xin AU - Cheng JX AUID- ORCID: 0000-0002-5607-6683 AD - Biomedical Engineering, Boston University, Boston, MA 02155, USA. AD - Electrical and Computer Engineering, Boston University, Boston, MA 02155, USA. AD - Photonics Center, Boston University, Boston, MA 02155, USA. LA - eng PT - Journal Article DEP - 20230816 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (Fatty Acids) RN - 7YNJ3PO35Z (Hydrogen) RN - 0 (Proteins) RN - 7440-44-0 (Carbon) SB - IM MH - Humans MH - *Neoplasms/drug therapy MH - Fatty Acids MH - Hydrogen MH - Proteins MH - Carbon MH - Spectrum Analysis, Raman/methods PMC - PMC10431717 EDAT- 2023/08/16 18:42 MHDA- 2023/08/18 06:42 PMCR- 2023/08/16 CRDT- 2023/08/16 14:04 PHST- 2023/08/18 06:42 [medline] PHST- 2023/08/16 18:42 [pubmed] PHST- 2023/08/16 14:04 [entrez] PHST- 2023/08/16 00:00 [pmc-release] AID - adg6061 [pii] AID - 10.1126/sciadv.adg6061 [doi] PST - ppublish SO - Sci Adv. 2023 Aug 18;9(33):eadg6061. doi: 10.1126/sciadv.adg6061. Epub 2023 Aug 16.