GSE107727
A single cell hematopoietic landscape resolves 8 lineage trajectories and defects in Kit mutant mice
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. Overall design: To determine the transcriptional landscape of mouse HSPCs in normal and perturbed haematopoiesis.