All cells in the hematopoietic system are generated from hematopoietic stem cells (HSCs) residing in the bone marrow. The HSCs give rise to progenitors that in turn give rise to gradually more specialized or comitted progeny that ultimately give rise to mature blood cells. Together the different developmental pathways form the hematopoietic developmental tree. The aim of the project is to understand the gene regulatory events that occur at developmental transitions and to understand how specific transcription factors control these processes. This is primarily persued using mouse models from which individual cells from discrete cellular stages can be identified and purified using FACS sorting. Both wild-type and transcription factor null mice are utilized. Hence, the proposed project aims to: 1 - Characterize hematopoietic developmental pathways and the gene regulatory changes occuring at such transitions. 2 – Pinpoint developmental deficiencies in transcription factor knock-out animals, and characterize the transcriptional dependencies that underpin the developmental failure. Both these aims will be persued using a combination of next-generation sequencing based approaches at the bulk (ChIPseq, ChIPmentation, RNAseq, ATACseq and HiC) or single cell level (scRNAseq and ATACseq). Together this will further our understanding of hematopoiesis and the gene regulatory networks that govern this continious developmental process.