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Peer-reviewedCC BY 4.0Cell Reports Methods

A sensitive method for profiling cell-type-specific secretomes of rare cells from complex tissues

  • Gergana Shipkovenska1
  • Xuchao Lyu2,3
  • Manalee Vishnu Surve1
  • Joao A. Paulo4
  • Edward Chen1
  • Vanshika Panchal1
  • Brian Lin5
  • Steven P. Gygi4
  • Wei Wei6
  • Jonathan Z. Long2,3,7
  • Jayaraj Rajagopal1
7 affiliations
  1. 1Department of Internal Medicine, Division of Pulmonary and Critical Care, Simches 4, Northeast Corridor, Massachusetts General Hospital, Boston, MA 02114, USA
  2. 2Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  3. 3Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA
  4. 4Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
  5. 5Department of Developmental, Molecular and Chemical Biology, School of Medicine, Tufts University, Boston, MA 02111, USA
  6. 6Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA
  7. 7The Phil & Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA
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Abstract

Very rare cells often have outsized physiologic functions. However, their low abundance presents a technical challenge for studying their function. Here, we generate a murine model, which enables the profiling of secreted proteomes (secretomes) from physiologically relevant low-abundance cells in complex tissues, without the use of viral vectors. We then deploy this model to profile the secretomes of two rare innate immune cell types: Kupffer macrophages from whole liver and the rare airway microfold (M) cells in cultures of differentiated airway epithelia. The method we have developed is characterized by remarkable sensitivity, capturing cell-specific proteins that were not captured in single-cell RNA sequencing (scRNA-seq) atlases. We have made this genetic secretome mouse model available to the community to empower future studies of cell-to-cell communication, secreted protein function, and biomarker discovery for any given cell type in vitro or in vivo.

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Cite

BibTeXRIS
BibTeX
@article{shipkovenska2026sensitive,
  title = {{A sensitive method for profiling cell-type-specific secretomes of rare cells from complex tissues}},
  author = {Gergana Shipkovenska and Xuchao Lyu and Manalee Vishnu Surve and Joao A. Paulo and Edward Chen and Vanshika Panchal and Brian Lin and Steven P. Gygi and Wei Wei and Jonathan Z. Long and Jayaraj Rajagopal},
  journal = {Cell Reports Methods},
  year = {2026},
  month = aug,
  doi = {10.1016/j.crmeth.2026.101552},
  url = {https://doi.org/10.1016/j.crmeth.2026.101552},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A sensitive method for profiling cell-type-specific secretomes of rare cells from complex tissues
AU  - Gergana Shipkovenska
AU  - Xuchao Lyu
AU  - Manalee Vishnu Surve
AU  - Joao A. Paulo
AU  - Edward Chen
AU  - Vanshika Panchal
AU  - Brian Lin
AU  - Steven P. Gygi
AU  - Wei Wei
AU  - Jonathan Z. Long
AU  - Jayaraj Rajagopal
PY  - 2026
DA  - 2026/08/14
JO  - Cell Reports Methods
DO  - 10.1016/j.crmeth.2026.101552
UR  - https://doi.org/10.1016/j.crmeth.2026.101552
AB  - Very rare cells often have outsized physiologic functions. However, their low abundance presents a technical challenge for studying their function. Here, we generate a murine model, which enables the profiling of secreted proteomes (secretomes) from physiologically relevant low-abundance cells in complex tissues, without the use of viral vectors. We then deploy this model to profile the secretomes of two rare innate immune cell types: Kupffer macrophages from whole liver and the rare airway microfold (M) cells in cultures of differentiated airway epithelia. The method we have developed is characterized by remarkable sensitivity, capturing cell-specific proteins that were not captured in single-cell RNA sequencing (scRNA-seq) atlases. We have made this genetic secretome mouse model available to the community to empower future studies of cell-to-cell communication, secreted protein function, and biomarker discovery for any given cell type in vitro or in vivo.
SN  - 2667-2375
ER  -