Deletion of Cebpa from HSCs

In this study, we use a conditional mouse model for Cebpa to investigate the significance of C/EBP in HSCs. The frequency of HSCs is unaltered following deletion of C/EBP, 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/EBP target genes by combining genome-wide C/EBP ChIP-seq analysis in stem and progenitor cells with gene expression data from HSC with and without C/EBP. Furthermore, we explore the impact of C/EBP 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/EBP.

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Hasemann MS, Lauridsen FK, Waage J, Jakobsen JS, Frank AK, Schuster MB, Rapin N, Bagger FO, Hoppe PS, Schroeder T, Porse BT