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.