Comprehensive spatial profiling of the spleen in murine and human myelofibrosis identifies targetable immune-stromal interactions

Data repository for the submission of the article "Comprehensive spatial profiling of the spleen in murine and human myelofibrosis identifies targetable immune-stromal interactions" Splenomegaly is a hallmark of myelofibrosis, yet the role of splenic mesenchymal stroma in MPN pathogenesis remains poorly understood. Using spatial and single-nucleus transcriptomics on MPN patient spleens, alongside single-cell RNA-seq and multiplex imaging in two murine myelofibrosis models, we describe the spleen remodeling in MPN into a hematopoietic and fibrotic organ, identifying the stromal niche as a therapeutic target. Finally, Visium HD data from murine myelofibrosis and C3 knockout models was employed to validate the effect of blocking our identified important cell cell interactions via C3 knockout. This repository contains the above mentioned processed datasets: updated_sn_RNAseq_human_export.qs single-nucleus transcriptomics on MPN patient spleens Relevant metadata columns: "Disease" (Healthy, MPN) "final_annotation" (annotation of the 14 main cell types) "final_annotation_high_res" (more detailed annotation with 21 cell types) Visium_human_export.Rds visium 10x spatial transcriptomics on MPN patient spleens Relevant metadata columns: "Disease" (the condition, Healthy, MPN) "Simplified_cluster" (final annotation without subclustering of the MPN-specific red pulp cluster) "Transferred_Annotations" (final annotation including subclustering of the MPN red pulp cluster) scRNAseq_mouse_Stroma_MPL_ThPO_EV.Rds single-cell transcriptomics on stromal compartment of MPL and ThPO murine myelofibrosis model spleens and control (EV) murine spleens. Relevant metadata columns: "stage" (the condition, EV, MPL, ThPO) "MPLThPOEV_anno" (final annotation) scRNAseq_mouse_Thpo_EV.Rds single-cell transcriptomics on ThPO murine myelofibrosis model spleens and control (EV) murine spleens. Relevant metadata columns: "stage" (the condition, EV, ThPO) "ECs_clustering" (final annotation) CODEX_run27-29_anndata_final_rev.h5ad CODEX protein intensity data from 3 runs (run27 - 29) , in total 11 samples from 3 different conditions: MPL and ThPO murine myelofibrosis model spleens and control (EV) murine spleens. Relevant metadata (obs) columns: "condition" (the condition, EV, ThPO, MPL) "clusters_named" (final annotation) VisiumHD_mouse_export.qs Visium HD data from ThPO murine myelofibrosis model spleens, control (EV) murine spleens, and C3 knockout model spleens for both of these conditions. Relevant metadata columns: "condition" (WTEV, WTThPO, C3KOEV, C3KOThPO) "Transferred_Annotations" (final annotation) Note for Rds file loading: #The following code should be run in R library(archive) load_object <- function(file_name){ con <- archive::file_read(file = file_name) res <- readRDS(file = con) close(con) return(res)} #and to load for example scRNAseq_mouse_Stroma_MPL_ThPO_EV.Rds object Seurat_object <- load_object("path/to/scRNAseq_mouse_Stroma_MPL_ThPO_EV.Rds")