Department of Hematology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Genes (Basel). 2023 Jul 27;14(8):1531. doi: 10.3390/genes14081531.
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 mice to clarify the role of deletion in hematopoiesis. Compared to mice, 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 mice and mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of cells were decreased relative to cells in all lineages. After the second BMT, neutrophils were few, while 20-30% of T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in HSPCs in a cleavage under targets and tagmentation assay. While deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that may play a role in the regulation of hematopoiesis.
UHRF 蛋白催化靶蛋白的泛素化，并参与调节基因表达。一些研究报道急性白血病细胞中 UHRF2 的表达降低，但 UHRF2 在造血中的作用尚不清楚。在这里，我们生成了 小鼠来阐明 缺失在造血中的作用。与 小鼠相比， 小鼠的全血细胞计数、骨髓（BM）发现和脾脏重量没有差异。BM 祖细胞分数中的细胞比例在 小鼠和 小鼠之间相似。然而，在 BM 移植（BMT）的竞争性重编程实验中，与 细胞相比，所有谱系中 细胞的比例均降低。第二次 BMT 后， 中性粒细胞很少，而仍检测到 20-30%的 T 细胞和 B 细胞。RNA 测序显示，一些与造血干细胞（HSPC）功能相关的基因在 HSPCs 中下调。有趣的是，在靶向切割和标签酶联测定中，UHRF2 缺失的 HSPCs 中组蛋白 H3 赖氨酸 9 的三甲基化增加。虽然 缺失不会导致血液恶性肿瘤或赋予 HSPCs 生长优势，但我们的结果表明， 可能在造血调控中发挥作用。
