A Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease
Year: 2026
Type: preprint
Abstract: Blood provides an accessible window into human health, yet the absence of a peripheral blood mononuclear cells (PBMCs) reference with standardized immune cell annotations has constrained comparisons between single-cell RNA sequencing (scRNAseq) studies. Here, we present HARP ( H uman Cell A tlas R eference for P BMCs), an integrated atlas of ∼9 million PBMCs from >2,600 donors across 15 studies spanning four continents, encompassing diverse populations, neonates to 97 years, across health and diverse immune-related diseases. We developed optimized integration workflows, including novel label-free metrics to assess integration quality, and generated community-driven consensus annotations for 192 immune cell subsets, identifying rare populations representing as few as 0.004% of PBMCs. HARP reveals coordinated cellular modules associated with age, sex, and disease, identifies female-biased interferon and inflammatory gene programs and their perturbation by COVID-19, and uncovers a novel sexual dimorphism in prostaglandin signaling. Finally, we introduce scTiger, a hierarchical label-transfer framework that accurately projects these 192 cell annotations onto ∼18 million additional PBMCs, providing a robust and transferable reference for harmonizing future PBMC studies. HARP provides a high-resolution community-driven reference atlas for PBMC annotation and analysis, as a basis for emerging clinical applications of single-cell genomics.
Authors: Ana-Maria Cujba, Sergio Aguilar-Fernandez, Adrien Antoinette, Wamia Said, Michaela F. Mueller, Kian Hong Kock, Jacquelyn Nestor, Radhika Sonthalia, Eliora V. Buyamin, Pragya Rawat, Alexander Predeus, Lorenz Kretschmer, Lijiang Fei, Kamil Slowikowski, Pritha Sen, Christopher V. Cosgriff, MGH COVID-19 Collection & Processing Team, Olli Dufva, Mohamad Askari, Kyle Kimler, Mary Futey, Ida Zucchi, Arsenios Chatzigeorgiou, Parisa Nejad, Liying Jin, Blake Bowen, Andrian Yang, Rik G. H. Lindeboom, Rachelly Normand, Stathis Megas, Yoshinari Ando, Ankita Chatterjee, Jong-Eun Park, Partha P. Majumder, Ponpan Matangkasombut, Varodom Charoensawan, Jay W. Shin, Woong-Yang Park, Asian Immune Diversity Atlas (AIDA) Network, Stephen Sansom, Berthold Göttgens, Joseph E. Powell, Lloyd Bod, Holger Heyn, Fabian J. Theis, Sarah A. Teichmann, Malte D. Luecken, Shyam Prabhakar, Alexandra-Chloé Villani, Gary Reynolds
Institutions: Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Broad Institute, Harvard University, Massachusetts General Hospital, Helmholtz Munich, Institute of Computational Biology, Technical University of Munich, Agency for Science, Technology and Research, Genome Institute of Singapore, Wellcome Sanger Institute, Sapienza University of Rome, Boston Children's Hospital, European Bioinformatics Institute, University of California, Santa Cruz, University of Oxford, Kennedy Institute of Rheumatology, Garvan Institute of Medical Research, UNSW Sydney, The Netherlands Cancer Institute, Medical University of Vienna, RIKEN Center for Integrative Medical Sciences, Korea Advanced Institute of Science and Technology, Indian Statistical Institute, Mahidol University, Siriraj Hospital, National University of Singapore, Sungkyunkwan University, Centro Nacional de Análisis Genómico, Canadian Institute for Advanced Research, German Center for Lung Research, National Cancer Centre Singapore
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1450308333, G6996855647, G8682988034
OpenAlex ID: W7214298271