A single-cell atlas of non-haematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling

The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here we constructed a single-cell transcriptome atlas of more than 100,000 NHCs collected from 27 human samples, including LNs and various nodal lymphomas, and it revealed 30 distinct subclusters, including some that were previously unrecognized. Notably, this atlas was useful for comparative analyses with lymphoma NHCs, which revealed an unanticipated landscape of subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs. This facilitates our understanding of stromal remodelling in lymphoma and highlights potential clinical biomarkers. Our study largely updates NHC taxonomy in human LNs and analysis of disease status, and provides a rich resource and deeper insights into LN and lymphoma biology to advance lymphoma management and therapy. Abe et al. profile, characterize and compare non-haematopoietic cells in normal human lymph nodes versus nodal lymphomas from patients, providing insights into stromal modelling in health and disease.

Automated summary

This study constructed a single-cell transcriptome atlas of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, collected from human samples. The atlas revealed 30 distinct subclusters of NHCs, including previously unrecognized ones. Comparative analyses with lymphoma NHCs showed subcluster-specific changes in gene expression and interaction with malignant cells in follicular lymphoma NHCs, providing insights into stromal remodelling in lymphoma and potential clinical biomarkers. The study updates NHC taxonomy in human lymph nodes and provides a rich resource for advancing lymphoma management and therapy.