13 May 2022

An “atlas” compiled with details of more than 100,000 non-haematopoietic cells (NHCs) has provided new insights into lymphoma stroma, Japanese researchers say.

Researchers from the University of Tsukuba collected the NHCs from 27 human samples, including lymph nodes and nodal lymphomas, encompassing follicular lymphomas and other lymphoma types. 

They used single-cell RNA sequencing to divide the NHCs into clusters and profile their gene expression. In doing so, the team discovered significant variation among these cells.

Writing in Nature Cell Biology, they say this heterogeneity was also detectable in aggressive lymphomas, which they believe suggests some of the subgroups could be involved in the progression of a tumour.

The team went on to identify a number of subgroups of NHCs, including some that were previously unrecognised, including specific types of endothelial cells.

Professor Mamiko Sakata-Yanagimoto, co-leader of the study with Prof Shigeru Chiba, said: “Once the atlas was developed, we performed differential gene expression analysis between subgroups in different types of lymph nodes affected by lymphoma and interestingly we found subcluster-specific transcriptional changes and a specific pattern of interaction with malignant cells in the stroma of follicular lymphomas.”

As follicular lymphomas are one of the most common types of lymphoma, having a gene expression signature and a prediction of how NHCs can interact with malignant cells could be useful to keep the tumour development under control.

The study also suggested that human lymph nodes have unique NHC subpopulations that have not been previously detected in mouse lymph nodes.

Prof Sakata-Yanagimoto said their findings have potential for therapeutic applications.

“This single-cell atlas of NHCs in human lymph nodes that we developed is applicable to lymphoma researchers all around the world,” he said.

“It can provide deep insights into lymphoma stromal biology and resources applicable to future studies on lymphomas, and also identify potential stroma-derived biomarkers that may serve as clinical indicators and/or therapeutic targets.”

Source: Abe Y, Sakata-Yanagimoto M, Fujisawa M, Miyoshi H, Suehara Y, Hattori K, Kusakabe M, Sakamoto T, Nishikii H, Nguyen TB, Owada Y, Enomoto T, Sawa A, Bando H, Yoshida C, Tabata R, Terao T, Nakayama M, Ohshima K, Usuki K, Oda T, Matsue K, Chiba S. (2022) “A single-cell atlas of non-hematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling.” Nature Cell Biology, doi: 10.1038/s41556-022-00866-3

Link: https://www.nature.com/articles/s41556-022-00866-3

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