Deletion of Cebpa from HSCs

In this study, we use a conditional mouse model for Cebpa to investigate the significance of C/EBPα in HSCs. The frequency of HSCs is unaltered following deletion of C/EBPα, however, upon serial transplantations of either full BM or purified HSCs, the stem cells and stem cell activity is lost. This is not due to increased proliferation, but rather caused by a shift from quiescence to apoptosis with a resultant exhaustion of the stem cell pool. We identify direct C/EBPα target genes by combining genome-wide C/EBPα ChIP-seq analysis in stem and progenitor cells with gene expression data from HSC with and without C/EBPα. Furthermore, we explore the impact of C/EBPα on active and repressive histone modifications by doing functional genome-wide ChIP-seq analysis of H3K4Me3 and H3K27Me3 in stem and progenitor cells with and without C/EBPα. We have sorted HSCs from 3 Cebpaflox/flox and 4 Cebpaflox/flox;Mx1Cre mice 18 days after pIC injection.