Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Hematopoietic stem cells differentiate into all types of blood cells, including peripheral tissue-resident mast cells. The early mast cell differentiation takes place in the bone marrow, after which the progenitor cells enter the circulation and mature once reaching their target organ. Early results from single-cell culture experiments and colony-forming assays have produced the classic hierarchical tree model of hematopoiesis. The introduction of high-throughput, single-cell RNA sequencing is now revolutionizing our understanding of the differentiation process, questioning the classic tree-based models. By integrating the results from early cell culture experiments with single-cell transcriptomics, we present a differentiation landscape model of hematopoiesis and discuss it with focus on mast cells. The review also describes how the hematologic neoplasm systemic mastocytosis can be used to model human hematopoiesis using naturally occurring cell barcoding by means of the common KIT D816V mutation.