Project description:Hematological malignancies develop through acquisition of mutations and clonal expansion in hematopoietic stem and progenitor cells (HSPCs). However, how individual mutations perturb the entire hematopoietic system towards malignant phenotypes remains elusive. Here, we have performed single cell RNA sequencing of bone marrow HSPCs from 8 different mutant mouse models to study mutation-specific preleukemic perturbations.
Project description:Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse) and models (in vivo/vitro) remains poorly inventoried at the single-cell-level. We single-cell RNA-sequenced 56,771 ECs from human/mouse (peri)-tumoral lung and cultured human lung TECs, detected 17 known and discovered 16 novel phenotypes, including TECs presumably regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a novel basement-membrane remodeling breach phenotype. Tip-TEC signatures correlated with patient-survival, and tip/breach TECs were most sensitive to VEGF-blockade. By similarity analysis, only tip-TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-seq data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen-modification as angiogenic candidate pathway.
Project description:Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse) and models (in vivo/vitro) remains poorly inventoried at the single-cell-level. We single-cell RNA-sequenced 56,771 ECs from human/mouse (peri)-tumoral lung and cultured human lung TECs, detected 17 known and discovered 16 novel phenotypes, including TECs presumably regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a novel basement-membrane remodeling breach phenotype. Tip-TEC signatures correlated with patient-survival, and tip/breach TECs were most sensitive to VEGF-blockade. By similarity analysis, only tip-TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-seq data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen-modification as angiogenic candidate pathway.
Project description:Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse) and models (in vivo/vitro) remains poorly inventoried at the single-cell-level. We single-cell RNA-sequenced 56,771 ECs from human/mouse (peri)-tumoral lung and cultured human lung TECs, detected 17 known and discovered 16 novel phenotypes, including TECs presumably regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a novel basement-membrane remodeling breach phenotype. Tip-TEC signatures correlated with patient-survival, and tip/breach TECs were most sensitive to VEGF-blockade. By similarity analysis, only tip-TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-seq data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen-modification as angiogenic candidate pathway.
Project description:Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse) and models (in vivo/vitro) remains poorly inventoried at the single-cell-level. We single-cell RNA-sequenced 56,771 ECs from human/mouse (peri)-tumoral lung and cultured human lung TECs, detected 17 known and discovered 16 novel phenotypes, including TECs presumably regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a novel basement-membrane remodeling breach phenotype. Tip-TEC signatures correlated with patient-survival, and tip/breach TECs were most sensitive to VEGF-blockade. By similarity analysis, only tip-TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-seq data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen-modification as angiogenic candidate pathway.