The normal human lymph node cell classification and landscape defined by high-dimensional spatial proteomics.
Overview
15 affiliations
- Istituto di Bioimmagini e Sistemi Biologici Complessi (IBSBC) – CNR Via F.lli Cervi, Segrate, Italy
- NBFC, National Biodiversity Future Center, Palermo, Italy
- Laboratorio di Data Science and Bioinformatics, IRCCS Istituto delle Scienze Neurologiche di Bologna – AUSL BO Ospedale Bellaria, Bologna, Italy
- Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy
- Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy
- The Leuven Institute for Single-cell Omics (LISCO), KULeuven, Leuven, Belgium
- Translational Cell and Tissue Research Unit, Department of imaging and pathology, KULeuven, Leuven, Belgium
- Pathology Department, University Hospital of Leuven, Leuven, Belgium
- Department of Immunobiology, Yale University, New Haven, Connecticut, United States of America
- Department of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America
- Pathology, Columbia University Irving Medical Center and New York Presbyterian Hospital, NewYork, New York, United States of America
- Department of Mathematics and Applications, University of Milano Bicocca, Milan, Italy
- Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
- Pathology, Department of Medicine and Surgery, Universitá di Milano-Bicocca, Monza, Michigan, Italy
Abstract
Lymph nodes (LN) are key secondary lymphoid organs (SLO) for a coordinated immune response. They have been extensively characterized by numerous investigative techniques chiefly as single cell suspensions because they are composed of vagile yet crowded hematolymphoid elements, unfriendly to spatial tissue organization-saving techniques. We comprehensively classify in situ all cells of 19 human LN free of pathology with a 78-marker antibody panel, an hyperplexed cyclic staining method, MILAN, and an analytical bioinformatic pipeline, BRAQUE. A total of 77 cell types were classified, encompassing T, B, innate immune and stromal cells. CD4 and CD8 T-cells were classified into 27 unique subsets by leveraging the expression profiles of TCF7, the presence of co-inhibitory receptors and the spatial distribution. CD5 and TCF7 expression defined novel B-cell types. CD27 + mature B-cells occupied previously unrecognized nodal spaces non-overlapping with the cortex and the plasma-cell rich medullary cords. Type 2 conventional dendritic cells were located in nodular paracortical aggregates. Statistically controlled pairwise neighborhood analysis showed sparse cell-cell interactions, known and new neighbors, established and novel LN landscape niches. A high-dimensional proteomic interrogation of the normal human LN provides spatial allocation of known cell types, novel interactions and the landscape organization.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- doi:10.17632/
3ntbp3zdzh.2 , at the source; found in the text, “High dimensional analysis with BRAQUE.”
Data Availability
This publication is part of the Human Cell Atlas - www.humancellatlas.org/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 MeSH terms, 10 funders, 143 references, 7 RRIDs.
Cite
This paper
Bolognesi, M. M., Dall’Olio, L., Mandelli, G. E., Lorenzi, L., Bosisio, F. M., Haberman, A. M., Bhagat, G., Borghesi, S., Faretta, M., Castellani, G., & Cattoretti, G. (2026). The normal human lymph node cell classification and landscape defined by high-dimensional spatial proteomics. PloS one, 21(4), e0346693. https://
BibTeX
@article{bolognesi2026no
author = {Bolognesi, Maddalena M and Dall’Olio, Lorenzo and Mandelli, Giulio Eugenio and Lorenzi, Luisa and Bosisio, Francesca M and Haberman, Ann M and Bhagat, Govind and Borghesi, Simone and Faretta, Mario and Castellani, Gastone and Cattoretti, Giorgio},
title = {{The normal human lymph node cell classification and landscape defined by high-dimensional spatial proteomics}},
journal = {PloS one},
year = {2026},
month = apr,
volume = {21},
number = {4},
pages = {e0346693},
publisher = {PLOS},
issn = {1932-6203},
doi = {10.1371/
url = {https://
pmid = {42013192},
pmcid = {PMC13099103}
}
RIS
TY - JOUR
AU - Bolognesi, Maddalena M
AU - Dall’Olio, Lorenzo
AU - Mandelli, Giulio Eugenio
AU - Lorenzi, Luisa
AU - Bosisio, Francesca M
AU - Haberman, Ann M
AU - Bhagat, Govind
AU - Borghesi, Simone
AU - Faretta, Mario
AU - Castellani, Gastone
AU - Cattoretti, Giorgio
TI - The normal human lymph node cell classification and landscape defined by high-dimensional spatial proteomics
T2 - PloS one
J2 - PLoS One
PY - 2026
DA - 2026/
VL - 21
IS - 4
SP - e0346693
SN - 1932-6203
PB - PLOS
DO - 10.1371/
UR - https://
LA - en
ER -
CSL-JSON
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