Hematopoiesis, where a single hematopoietic stem cell gives rise to the entire blood system, is an important model for differentiation with great medical importance. While the hematopoietic system is perhaps the most characterized model system of cellular commitment and differentiation, we currently lack understanding as to the prevalence of heterogeneity in progenitor populations.

In a recent work, we took an important first step towards unbiased characterization of hematopoiesis decisions, by measuring and modeling chromatin state dynamics during hematopoietic development. These detailed chromatin maps pointed to large discrepancies between the common hematopoietic tree and the enhancer profiles we uncovered. I will discuss how using massively parallel single cell RNA-seq we find unexpected developmental states and heterogeneity among hematopoietic progenitor populations and the regulatory circuits driving hematopoietic decisions. Together, these result show that lineage commitment in hematopoiesis likely occur earlier then appreciated before and highlight the importance of further exploration of developmental decisions using single cell genome-wide approaches.