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

Abstract

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.

Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma

“…Of note, ANXA1, FPR1, and FPR2 were not differentially expressed in FL samples compared to rLN in published datasets of stromal, endothelial, T, and B cells. 7,9 ANXA1 is an anti-inflammatory calcium-regulated protein, whose only know receptors are the FPR G-protein coupled PRR formyl-peptide receptors. ANXA1-FPR interaction is involved in monocyte recruitment and polarization, switching them to an M2/reparative/pro-tumor phenotype.…”

“…1 Composition and organization of the immune and nonimmune tumor microenvironment (TME) have been progressively identified as crucial in supporting FL and DLBCL tumor growth and resistance to treatment. [2][3][4][5] Landscape of tumorinfiltrating T-cells and stromal cells has been explored at the single cell level in DLBCL and FL [6][7][8][9] but the heterogeneity of the myeloid compartment still remains essentially uncharacterized, mainly due to the technical limitations of the classically used non-enzymatic lymph node (LN) dissociation approaches.…”

POSTRE: a tool to predict the pathological effects of human structural variants

“…In addition to the problem of using bulk data from heterogeneous tissues, the lack of genomic data for the appropriate developmental stages or differentiation time points may also affect the identification of pathologically relevant genes. Nevertheless, recent advances in single-cell genomics are expected to dramatically expand the catalogue of cell types and developmental stages in which gene expression profiles and enhancer maps can be explored (Abe et al, 2022; Eraslan et al, 2022; Tabula Sapiens Consortium* et al, 2022). Therefore, as single-cell datasets are generated in human embryos and incorporated to POSTRE, the tool will be capable of handling additional congenital abnormalities and also its sensitivity will increase. One major discussion in the field of data sciences, particularly in the health care area, is model interpretability (Lipton, 2016; Reddy, 2022).…”

Integrated single cell analysis reveals co-evolution of malignant B cells and the tumor microenvironment in transformed follicular lymphoma

“…Using two independent cohorts, we could validate that the level of infiltration of LAG3+CD8+ cells before treatment initiation, within the TME, was a predictive marker of transformation and outcome. Other recent single-cell FL reports have also highlighted a key role of tumour microenvironment (TME) (Abe et al, 2022) B cell plasticity and attempted to develop a classification based on T cell subsets (Han et al, 2022), but our single cell study is the first one to show that implementation of single cell techniques in tFL prediction is valuable. The role of regulatory TME cells in transformation and outcome has already been assessed, primarily using bulk sequencing, and has resulted in inconsistent results on FL prognosis (Alcoceba et al, 2022; Casulo, 2021; Mondello et al, 2021).…”