Impaired Repopulating Ability of Uhrf2^-/- Hematopoietic Progenitor Cells in Mice

UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated Uhrf2 mice to clarify the role of UHRF2 deletion in hematopoiesis. Compared to Uhrf2 mice, Uhrf2 mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between Uhrf2 mice and Uhrf2 mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of Uhrf2 cells were decreased relative to Uhrf2 cells in all lineages. After the second BMT, Uhrf2 neutrophils were few, while 20-30% of Uhrf2^-/- T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in Uhrf2 hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in Uhrf2 HSPCs in a cleavage under targets and tagmentation assay. While UHRF2 deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that UHRF2 may play a role in the regulation of hematopoiesis.