Department of Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Nat Cell Biol. 2022 Apr;24(4):565-578. doi: 10.1038/s41556-022-00866-3. Epub 2022 Mar 24.
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.
非造血细胞（NHC）的活性，包括间充质基质细胞和内皮细胞，据报道是淋巴瘤发生的基础。然而，由于未解释的 NHC 异质性，即使在正常人类淋巴结（LN）中，我们对淋巴瘤 NHC 的理解也受到了阻碍。在这里，我们构建了一个超过 100,000 个 NHC 的单细胞转录组图谱，这些 NHC 来自 27 个人体样本，包括 LN 和各种结内淋巴瘤，它揭示了 30 个不同的亚群，包括一些以前未被识别的亚群。值得注意的是，这个图谱对于与滤泡性淋巴瘤 NHC 的比较分析非常有用，这揭示了滤泡性淋巴瘤 NHC 中基因表达和与恶性细胞相互作用的亚群特异性变化的意外景观。这有助于我们理解淋巴瘤中的基质重塑，并突出潜在的临床生物标志物。我们的研究在很大程度上更新了人类 LN 中的 NHC 分类和疾病状态分析，并为 LN 和淋巴瘤生物学提供了丰富的资源和更深入的见解，以推进淋巴瘤的管理和治疗。
