In hematopoiesis rare hematopoietic stem cells (HSC) form all the cellular components of the blood. The HSC compartment is functionally heterogeneous, consisting of biased HSCs with different preferences to generate mature blood cells. In aging, lineage-biased HSCs are dynamically changed. In leukemia, HSCs are often the cellular origin of leukemic stem cells. However, the mechanisms underlying HSC lineage bias and how it affects aging and leukemic processes are not well studied. Our hypothesis is that there are gene expression and epigenetic differences in lineage-biased HSCs that influence both aging and leukemia development. In this project, our aim is to isolate lineage-biased HSCs from young and old mice and from normal and leukemic mice to investigate the transcriptome by RNA-seq, chromatin accessibility by ATAC-seq and the proteome by proteomics analysis to create comprehensive molecular profiles of distinct HSC subsets in aging and in leukemia. The project will provide important insights into the HSC heterogeneity and its role in aging and leukemic processes. Bioinformatics will be done in house with our collaborator and co-investigator Dr. Robert Månsson's group at Karolinska Institutet.