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Peer-reviewedCC BY-NC-NDNature communications

Cell-type-specific surfaceome profiling of 100-500 isolated cells using a droplet-based Magnetic Affinity Purification System.

1 more authors
6 affiliations
  1. 1Department of Proteomic & Genomic Technologies, Genentech Inc., South San Francisco, CA, USA.
  2. 2Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA.
  3. 3Department of Research Pathology, Genentech Inc., South San Francisco, CA, USA.
  4. 4Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA.
  5. 5Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA. [email protected].
  6. 6Department of Proteomic & Genomic Technologies, Genentech Inc., South San Francisco, CA, USA. [email protected].

Abstract

Cell surface proteins represent an important source of biomarkers and therapeutic targets. However, due to the inherent sensitivity limitations of existing technologies, tissue and cell-type-specific surfaceomes remain poorly characterized, especially in the context of human diseases. Here, we present nanoMAPS (nanoscale Magnetic Affinity Purification System), a miniaturized proteomic sample preparation method for surfaceome profiling of as few as 100-500 cells (~100,000-fold lower than existing technologies). By performing magnetic bead-based affinity purification within a single microliter-scale droplet, nanoMAPS significantly improves the recovery of surface proteins and reduces non-specific absorption of intracellular proteins. Application of nanoMAPS to primary human immune cells and mouse plasma cell populations enables robust identification of established cell-type-specific surface markers as well as other proteins selectively enriched in disease-associated immune cell subpopulations. Together, these results establish nanoMAPS as a broadly applicable platform for extending surface proteomics technology to rare primary cells isolated directly from diseased tissues.

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BibTeX
@article{lorentzian2026celltypespecific,
  title = {{Cell-type-specific surfaceome profiling of 100-500 isolated cells using a droplet-based Magnetic Affinity Purification System.}},
  author = {Amanda C Lorentzian and Juliet M Bartleson and Terence Ho and Hao Xu and Christopher B Bullock and Zhichang Yang and Alan G Gutierrez and Meena Choi and Tommy K Cheung and Christopher M Rose and Hua Zhang and William T Yewdell and Ying Zhu},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77876-4},
  url = {https://europepmc.org/article/MED/42901912},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Cell-type-specific surfaceome profiling of 100-500 isolated cells using a droplet-based Magnetic Affinity Purification System.
AU  - Amanda C Lorentzian
AU  - Juliet M Bartleson
AU  - Terence Ho
AU  - Hao Xu
AU  - Christopher B Bullock
AU  - Zhichang Yang
AU  - Alan G Gutierrez
AU  - Meena Choi
AU  - Tommy K Cheung
AU  - Christopher M Rose
AU  - Hua Zhang
AU  - William T Yewdell
AU  - Ying Zhu
PY  - 2026
DA  - 2026/09/18
JO  - Nature communications
DO  - 10.1038/s41467-026-77876-4
UR  - https://europepmc.org/article/MED/42901912
AB  - Cell surface proteins represent an important source of biomarkers and therapeutic targets. However, due to the inherent sensitivity limitations of existing technologies, tissue and cell-type-specific surfaceomes remain poorly characterized, especially in the context of human diseases. Here, we present nanoMAPS (nanoscale Magnetic Affinity Purification System), a miniaturized proteomic sample preparation method for surfaceome profiling of as few as 100-500 cells (~100,000-fold lower than existing technologies). By performing magnetic bead-based affinity purification within a single microliter-scale droplet, nanoMAPS significantly improves the recovery of surface proteins and reduces non-specific absorption of intracellular proteins. Application of nanoMAPS to primary human immune cells and mouse plasma cell populations enables robust identification of established cell-type-specific surface markers as well as other proteins selectively enriched in disease-associated immune cell subpopulations. Together, these results establish nanoMAPS as a broadly applicable platform for extending surface proteomics technology to rare primary cells isolated directly from diseased tissues.
SN  - 2041-1723
ER  -