Impaired Repopulating Ability of Uhrf2−/− Hematopoietic Progenitor Cells in Mice

• Published in: Genes Vol. 14; no. 8; p. 1531
• Main Authors: Sano, Takahiro, Ueda, Koki, Minakawa, Keiji, Mori, Tsutomu, Hashimoto, Yuko, Koseki, Haruhiko, Takeishi, Yasuchika, Ikeda, Kazuhiko, Ikezoe, Takayuki
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27.07.2023; MDPI
• Subjects: Bone marrow; Cancer; Competition; Flow cytometry; Gene expression; Genomes; Genotype & phenotype; hematopoiesis; hematopoietic stem and progenitor cells; Hematopoietic stem cells; Hemopoiesis; Histone H3; Histones; Leukocytes (neutrophilic); Lymphocytes B; Lymphocytes T; Malignancy; Progenitor cells; Proteins; Transplants & implants; Ubiquitination; UHRF2; United States > US; Japan
• ISSN: 2073-4425; 2073-4425
• 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 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.