Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Eur J Immunol. 2023 Sep;53(9):e2250362. doi: 10.1002/eji.202250362. Epub 2023 Jun 27.
Nonhematopoietic lymph node stromal cells (LNSCs) regulate lymphocyte trafficking, survival, and function for key roles in host defense, autoimmunity, alloimmunity, and lymphoproliferative disorders. However, the study of LNSCs in human diseases is complicated by a dependence on viable lymphoid tissues, which are most often excised prior to establishment of a specific diagnosis. Here, we demonstrate that cryopreservation can be used to bank lymphoid tissue for the study of LNSCs in human disease. Using human tonsils and lymph nodes (LN), lymphoid tissue fragments were cryopreserved for subsequent enzymatic digestion and recovery of viable nonhematopoietic cells. Flow cytometry and single-cell transcriptomics identified comparable proportions of LN stromal cell types in fresh and cryopreserved tissue. Moreover, cryopreservation had little effect on transcriptional profiles, which showed significant overlap between tonsils and LN. The presence and spatial distribution of transcriptionally defined cell types were confirmed by in situ analyses. Our broadly applicable approach promises to greatly enable research into the roles of LNSCs in human disease.
非造血性淋巴结基质细胞(LNSCs)在宿主防御、自身免疫、同种免疫和淋巴增生性疾病中调节淋巴细胞的迁移、存活和功能,发挥着关键作用。然而,由于依赖于有活力的淋巴组织,LNSCs 在人类疾病中的研究变得复杂,这些组织通常在确定特定诊断之前被切除。在这里,我们证明了可以通过冷冻保存来储存淋巴组织,以便研究人类疾病中的 LNSCs。我们使用人扁桃体和淋巴结(LN),将淋巴组织碎片冷冻保存,以备后续进行酶消化和回收有活力的非造血细胞。流式细胞术和单细胞转录组学鉴定了新鲜和冷冻保存组织中 LN 基质细胞类型的比例相当。此外,冷冻保存对转录谱的影响很小,扁桃体和 LN 之间有显著的重叠。通过原位分析证实了转录定义的细胞类型的存在和空间分布。我们广泛适用的方法有望极大地促进对 LNSCs 在人类疾病中的作用的研究。