Spatial transcriptomic data of a lymph node from an individual with Multicentric Castleman Disease

Idiopathic Multicentric Castleman Disease (iMCD) is a rare IL-6-driven hematological disorder characterized by systemic lymphadenopathy, elevated immunoglobulin levels, and prominent plasmacytosis in the bone marrow and lymph nodes. Here, we present an unusual occurrence of iMCD in identical twins. Using single cell sequencing, we identified nodal endothelial cells and fibroblastic reticular cells as the source of IL-6 signals. An “inflammatory” peripheral monocytosis enriched for the expression of S100A family genes was evident in both twins, as well as a group of monocytes expressing cytotoxic gene signatures in the affected twin with milder clinical manifestations. Overall design: To spatially resolve the transcriptome of the lymph node from Twin-CS, we applied Spatial Enhanced Resolution Omics-Sequencing (Stereo-seq), involving the use of DNA nanoball (DNB)-patterned arrays and in situ RNA capture. Stereo-seq provides a large field of view spatial transcriptomics at cellular resolution. The lymph node tissue was embedded with pre-chilled Tissue-Tek optimum cutting temperature (OCT) compound (Sakura, 4583) and snap-frozen in liquid nitrogen until the OCT was completely solid, before long term storage at -80°C. The tissue was cryosectioned at a thickness of 10 µm and then placed in a pre-chilled Stereo-seq capture chip, and libraries were prepared following the standard manufacturer's protocol as previously described (MiRXES, Singapore).