A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice.
American Society of Hematology
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Dahlin, J. S., Hamey, F., Pijuan-Sala, B., Shepherd, M., Lau, W., Shaw, S., Weinreb, C., et al. (2018). A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice.. Blood, 131 (21), e1-e11. https://doi.org/10.1182/blood-2017-12-821413
Hematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system and their dysregulation causes a multitude of diseases. However, the differentiation journeys towards 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 eight 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 pro-apoptotic 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.
Bone Marrow Cells, Hematopoietic Stem Cells, Cells, Cultured, Cell Line, Tumor, Animals, Mice, Knockout, Mice, Gene Expression Profiling, Signal Transduction, Cell Differentiation, Cell Lineage, Mutation, Proto-Oncogene Proteins c-kit, Single-Cell Analysis, Transcriptome
Leukaemia & Lymphoma Research (12029)
Cancer Research UK (21762)
National Institutes of Health (NIH) (via Pennsylvania State University) (R24DK106766)
Wellcome Trust (206328/Z/17/Z)
MEDICAL RESEARCH COUNCIL (MR/M008975/1)
External DOI: https://doi.org/10.1182/blood-2017-12-821413
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277710