EasySCP unveils extensive liver zonation at single-cell proteomics resolution

  • Nat Commun. 2026 Jun 16. doi: 10.1038/s41467-026-74525-8.
Bingbing Hao  #  1  2 ,  Jinghui Wei  #  3  4  5 ,  Jiaen Xu  3 ,  Ying Fu  6 ,  Qiaoyu Zou  5 ,  Xu Wang  5 ,  Siyu Wang  5 ,  Yixuan Shi  7 ,  Yale Chen  7 ,  Ken Xie  8 ,  Xun Huang  3  9 ,  Tong-Jin Zhao  3  4  10 ,  Zigang Dong  3  4  7 ,  Peng Li  3  4 ,  Guochen Qin  11 ,  Ido Amit  12 ,  Baoguo Li  13  14
Affiliations
  • 1. State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, School of Convergence Medicine, Zhengzhou University, Zhengzhou, China. [email protected].
  • 2. Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China. [email protected].
  • 3. State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, School of Convergence Medicine, Zhengzhou University, Zhengzhou, China.
  • 4. Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China.
  • 5. School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  • 6. Peking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences at Weifang, Weifang, Shandong, China.
  • 7. School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, China.
  • 8. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • 9. Taikang Center for Life and Medical Sciences, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
  • 10. Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • 11. Peking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences at Weifang, Weifang, Shandong, China. [email protected].
  • 12. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. [email protected].
  • 13. State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, School of Convergence Medicine, Zhengzhou University, Zhengzhou, China. [email protected].
  • 14. Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China. [email protected].
  • # Contributed equally.
PMID: 42303986 DOI: 10.1038/s41467-026-74525-8
Abstract

The broader application of single-cell proteomics (SCP) in biology has been limited by complex workflows and reliance on specialized instrumentation. Here we present EasySCP, a high-throughput method that integrates FACS-based single-cell sorting, an all-in-one, single-step digestion process in 384-well plates, and sensitive mass spectrometry. EasySCP identifies nearly 5000 proteins from individual HEK293 cell. Applied to female murine liver, EasySCP achieves spatially informed proteomics profiling of hepatocytes zonation, detecting an average of 3500 proteins per hepatocyte and uncovering zonation patterns for 3277 out of 5267 proteins. Building on 215 conserved zonation markers, we further develop hepatocyte spatial status score (HSS) that enables reconstruct liver zonation across single-cell and multi-omics datasets. Together, our study introduces EasySCP, a broadly accessible tool for dissecting cellular heterogeneity at single-cell proteomics resolution in both healthy and disease states, effectively bridging the gap between transcriptomics and functional proteomics.

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