Project description:Human tissues harbour a wide array of cellular populations, often including both immune and lymphoid cell populations, endothelial cells and fibroblasts. The goal of this study was to identify transcriptomic markers of these cell populations, in order to quantify their abundances using transcriptomic data. The present super-series is composed of a large number of transcriptomic profiles of these cell populations. These profiles were obtained from public repositories, normalized using the fRMA R package (which allows a consistent normalization of profiles across public series), and consistently annotated. This series corresponds to Affymetrix 133 A profiles. Sample's annotation is available as supplementary material.
Project description:Human tissues harbour a wide array of cellular populations, often including both immune and lymphoid cell populations, endothelial cells and fibroblasts. The goal of this study was to identify transcriptomic markers of these cell populations, in order to quantify their abundances using transcriptomic data. The present super-series is composed of a large number of transcriptomic profiles of these cell populations. These profiles were obtained from public repositories, normalized using the fRMA R package (which allows a consistent normalization of profiles across public series), and consistently annotated. This series corresponds to Affymetrix HuGene 1.0ST profiles. Sample's annotation is available as supplementary material.
Project description:Human tissues harbour a wide array of cellular populations, often including both immune and lymphoid cell populations, endothelial cells and fibroblasts. The goal of this study was to identify transcriptomic markers of these cell populations, in order to quantify their abundances using transcriptomic data. The present super-series is composed of a large number of transcriptomic profiles of these cell populations. These profiles were obtained from public repositories, normalized using the fRMA R package (which allows a consistent normalization of profiles across public series), and consistently annotated. This series corresponds to Affymetrix 133 Plus 2.0 profiles. Sample's annotation is available as supplementary material.
Project description:High-risk neuroblastoma is a pediatric cancer with dismal prognosis. In this study, we have used various approaches including single-cell RNA sequencing to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of biopsies from neuroblastoma patients. From the diverse cell populations identified, our data document a striking correspondence of the microenvironment populations between tumors from both species and unravel a complex content in myeloid cells and cancer-associated fibroblasts. Within the myeloid compartment we have characterized a population of cells exhibiting features of tumor-associated neutrophils and demonstrate that these cells obtained from the mouse model have immunosuppressive properties. Altogether, our study shows that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T-cells and accumulation of immunosuppressive cells. Our data provide the rationale for novel immunotherapeutic strategies in neuroblastoma, targeting both tumor cells and components of its microenvironment.
Project description:To define alterations early in tumor formation, we studied nerve tumors in neurofibromatosis 1 (NF1), a tumor predisposition syndrome in which affected individuals develop plexiform neurofibroma (PN). These benign tumors are driven by NF1 loss in Schwann cells (SC). By comparing normal nerve cells to PN cells using single cell and bulk RNA sequencing, we identified changes in five SC populations, including a de novo Schwann cell progenitor-like population. Long after Nf1 loss, SC populations developed PN-specific expression of Dcn, Postn, and CD74, and showed dramatic expansion of immune and stromal cell populations; in human PN, immune and stromal cells comprised 90% of cells. Label transfer enabled verification of each SC population and predicted tumor unique patterns of cell-cell communication in each SC population. We identified PROS-AXL, FGF-FGFR, and MIF-CD74 and its effector pathway NFkB as deregulated in NF1 SC populations, including SCP-like cells. Each receptor-ligand pair was predicted to influence surrounding cells in mouse and human. These findings highlight remarkable changes in all PN cells driven by loss of NF1 in multiple types of SCs and identify therapeutic targets for PN.