A single cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
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PROVIDER: PRJNA421199 | ENA |
REPOSITORIES: ENA
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Project description:Haematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system and their dysregulation causes a multitude of diseases. However, the differentiation journeys towards specific haematopoietic lineages remain ill defined, and system-wide disease interpretation remains challenging. Here, we have profiled 44,802 mouse bone marrow HSPCs using single cell RNA-Sequencing to provide a comprehensive transcriptional landscape with entry points to eight different blood lineages. We identified a common basophil/mast cell bone marrow progenitor, and characterised its molecular profile at the single cell level. Transcriptome sequencing of 13,815 HSPCs from the c-kit mutant W41 mouse model revealed the lack of a distinct mast cell lineage entry point, together with global shifts in cell type abundance. Proliferative defects were accompanied by reduced Myc expression. Compensatory processes included upreglation of the integrated stress response pathway and downregulation of pro-apoptotic gene expression in erythroid progenitors, thus providing a template of how single cell transcriptomics can reveal qualitative, quantitative and molecular aspects of mutant phenotypes.
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Project description:Hematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system, and their dysregulation causes a multitude of diseases. However, the differentiation journeys toward specific hematopoietic lineages remain ill defined, and system-wide disease interpretation remains challenging. Here, we have profiled 44?802 mouse bone marrow HSPCs using single-cell RNA sequencing to provide a comprehensive transcriptional landscape with entry points to 8 different blood lineages (lymphoid, megakaryocyte, erythroid, neutrophil, monocyte, eosinophil, mast cell, and basophil progenitors). We identified a common basophil/mast cell bone marrow progenitor and characterized its molecular profile at the single-cell level. Transcriptional profiling of 13 815 HSPCs from the c-Kit mutant (W41/W41) mouse model revealed the absence of a distinct mast cell lineage entry point, together with global shifts in cell type abundance. Proliferative defects were accompanied by reduced Myc expression. Potential compensatory processes included upregulation of the integrated stress response pathway and downregulation of proapoptotic gene expression in erythroid progenitors, thus providing a template of how large-scale single-cell transcriptomic studies can bridge between molecular phenotypes and quantitative population changes.
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