PROJECTS

The tumour microenvironment (TME) is a complex ecosystem composed of stromal and cancer cells. The stromal compartment is highly heterogeneous, consisting of tissue-resident and tumour-infiltrating cells, both of which are profoundly moulded by cancer cells. An outstanding question is to what extent this stromal cell heterogeneity is similar between cancers affecting different organs. Here, we profiled the transcriptomes of more than 233,000 single cells from patients with lung, colorectal, ovary and breast cancer (n=36) and constructed a pan-cancer blueprint of stromal cell heterogeneity. We overall identified 68 stromal cell phenotypes, of which 46 were shared between cancer types and 22 were cancer type-unique. Most cell phenotypes have previously not been characterized in detail at single-cell level. By providing such comprehensive blueprint, we generated a first detailed view on the shared complexity of stromal cells in different cancers.

• An in-depth anlysis(manuscript) and the associed pan-cancer blueprint datasets were listed below:
• Pan-cancer blueprint of the heterogeneous tumour microenvironment revealed by single-cell profiling, Qian et al.,Cell Res (2020).
  • Clustering per cancer type
    • 8 lung cancer patients (93,575 cells), 3 prime scRNA-seq  Fig. 1b (LC)-- Download: [Counts matrix] - [Metadata]
    • 7 colorectal cancer patents (44,684 cells), 3 prime scRNA-seq Fig. 1b (CRC)-- Download: [Counts matrix] - [Metadata]
    • 5 ovarian cancer patents (45,114 cells), 3 prime scRNA-seq Fig. 1b (OvC)-- Download: [Counts matrix] - [Metadata]
    • 14 breast cancer patents (44,024 cells), 5 prime scRNA-seq Fig. 8a (BC)-- Download: [Counts matrix] - [Metadata]
  • Clustering per stromal cell type
    • Endothelial cells (9,476 cells): Fig. 2a (unaligned - 3 tissues), Fig. 2a (CCA aligned - 3 tissues) , Fig. S9c (CCA aligned - 4 tissues)
    • Fibroblasts (30,292 cells): Fig. 3a (unaligned - 3 tissues), Fig. 3c (CCA aligned - 3 tissues) , Fig. S9c (CCA aligned - 4 tissues)
    • Dendritic cells (3,084 cells): Fig. 4a (unaligned - 3 tissues), Fig. 4a (CCA aligned - 3 tissues) , Fig. 8c (CCA aligned - 4 tissues)
    • B cells (17,944 cells): Fig. 5a (unaligned - 3 tissues), Fig. 5a (CCA aligned - 3 tissues) , Fig. S9c (CCA aligned - 4 tissues)
    • T cells (66,889 cells): Fig. 6a (unaligned - 3 tissues), Fig. 6a (CCA aligned - 3 tissues) , Fig. 8b (CCA aligned - 4 tissues)
    • Myeloid cells (monocytes, macrophages, neutrophils, 34,686 cells): Fig. 7a (unaligned - 3 tissues), Fig. S7c (CCA aligned - 3 tissues) ,Fig. S9c (CCA aligned - 4 tissues)
    • Mast cells (1,962 cells): Fig. S8a (unaligned - 3 tissues)
• High-grade serous tubo-ovarian cancer refined with single-cell RNA-sequencing: specific cell subtypes influence survival and determine molecular subtype classification., Olbrecht et al., under revision (2021).
  • [Counts matrix] - [Metadata] - [Seurat scripts]

For more information, please visit our website at VIB The Laboratory of Translational Genetics

The single-cell RNA-seq dataset visualization is based on SCope developed by Stein Aerts lab.

• SARS-CoV-2 has rapidly swept across the globe affecting >33 million people, with >1 million fatal cases. It is now well appreciated that while most COVID-19 patients (80%) remain asymptomatic or experience only mild symptoms, 20% present with overt pneumonia; about a quarter of these progressing to life-threatening Acute Respiratory Distress Syndrome (ARDS) and severe or atypical systemic inflammation. Fever, increased acute phase reactants and coagulopathy with decreased lymphocyte counts, pronounced myeloid inflammation and increased neutrophil-to-lymphocyte ratio are predominant immunological hallmarks of critical COVID-19. 
  How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we provide a comprehensive deep-immune atlas of COVID-19 pneumonia, analyzing BAL from 31 COVID-19 patients with mild or critical disease, while inclusion of 13 patients with non-COVID-19 pneumonia allowed us to reliably distinguish non-specific lung-localized inflammatory signaling from COVID-19 specific lung-associated immune changes.

• An in-depth analysis (manuscript) and the associated COVID-19 BAL datasets were listed below:
• Discriminating Mild from Critical COVID-19 by Innate and Adaptive Immune Single-cell Profiling of Bronchoalveolar Lavages , Wauters et al., (manuscript accepted, 2020)
  • Clustering all cels 
    • 22 COVID-19 patients and 13 non-COVID-19 patients, 5 prime scRNA-seq:  [Counts matrix] - [Metadata]
  • Clustering per cell type
    • T-/NK-cell cells : [Counts matrix] - [Metadata]
    • Monocyte/macrophage : [Counts matrix] - [Metadata]
    • Neutrophils: [Counts matrix] - [Metadata]
    • Dendritic cells: [Counts matrix] - [Metadata]
    • B-/plasma-cells: [Counts matrix] - [Metadata]
    • Epithelial cells: [Counts matrix] - [Metadata]
• Our data (Seurat object) were used in "Genome-wide CRISPR screening identifies TMEM106B as proviral host factor for SARS-CoV-2" (Baggen et al., Nature Genetics, 2021). To illustrate the TMEM106B expression in epithelial cells from human airways correlates with SARS-CoV-2 infection. 
• PBMC data of 10 (severe) and 13 (mild) COVID-19 patients were used in "Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity" (Nat. Comm., 2021).  [Counts matrix] - [Metadata]

For more information, please visit our website at VIB The Laboratory of Translational Genetics