Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> 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 <i>Uhrf2<sup>−/−</sup>...
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MDPI AG
2023-07-01
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| author | Takahiro Sano Koki Ueda Keiji Minakawa Tsutomu Mori Yuko Hashimoto Haruhiko Koseki Yasuchika Takeishi Kazuhiko Ikeda Takayuki Ikezoe |
| author_facet | Takahiro Sano Koki Ueda Keiji Minakawa Tsutomu Mori Yuko Hashimoto Haruhiko Koseki Yasuchika Takeishi Kazuhiko Ikeda Takayuki Ikezoe |
| author_sort | Takahiro Sano |
| collection | DOAJ |
| description | 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 <i>Uhrf2<sup>−/−</sup></i> mice to clarify the role of <i>UHRF2</i> deletion in hematopoiesis. Compared to <i>Uhrf2<sup>+/+</sup></i> mice, <i>Uhrf2<sup>−/−</sup></i> 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 <i>Uhrf2<sup>+/+</sup></i> mice and <i>Uhrf2<sup>−/−</sup></i> mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of <i>Uhrf2<sup>−/−</sup></i> cells were decreased relative to <i>Uhrf2<sup>+/+</sup></i> cells in all lineages. After the second BMT, <i>Uhrf2<sup>−/−</sup></i> neutrophils were few, while 20–30% of <i>Uhrf2</i><sup>−/−</sup> T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in <i>Uhrf2<sup>−/−</sup></i> hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in <i>Uhrf2<sup>−/−</sup></i> HSPCs in a cleavage under targets and tagmentation assay. While <i>UHRF2</i> deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that <i>UHRF2</i> may play a role in the regulation of hematopoiesis. |
| first_indexed | 2024-03-10T23:55:28Z |
| format | Article |
| id | doaj.art-9279633293a149ae91256b0fa13d77c7 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T23:55:28Z |
| publishDate | 2023-07-01 |
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| series | Genes |
| spelling | doaj.art-9279633293a149ae91256b0fa13d77c72023-11-19T01:14:32ZengMDPI AGGenes2073-44252023-07-01148153110.3390/genes14081531Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in MiceTakahiro Sano0Koki Ueda1Keiji Minakawa2Tsutomu Mori3Yuko Hashimoto4Haruhiko Koseki5Yasuchika Takeishi6Kazuhiko Ikeda7Takayuki Ikezoe8Department of Hematology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Human Life Sciences; Fukushima Medical University School of Nursing, Fukushima 960-1295, JapanDepartment of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Wako 351-0198, JapanDepartment of Cardiovascular Medicine, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanDepartment of Hematology, Fukushima Medical University School of Medicine, Fukushima 960-1295, JapanUHRF 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 <i>Uhrf2<sup>−/−</sup></i> mice to clarify the role of <i>UHRF2</i> deletion in hematopoiesis. Compared to <i>Uhrf2<sup>+/+</sup></i> mice, <i>Uhrf2<sup>−/−</sup></i> 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 <i>Uhrf2<sup>+/+</sup></i> mice and <i>Uhrf2<sup>−/−</sup></i> mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of <i>Uhrf2<sup>−/−</sup></i> cells were decreased relative to <i>Uhrf2<sup>+/+</sup></i> cells in all lineages. After the second BMT, <i>Uhrf2<sup>−/−</sup></i> neutrophils were few, while 20–30% of <i>Uhrf2</i><sup>−/−</sup> T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in <i>Uhrf2<sup>−/−</sup></i> hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in <i>Uhrf2<sup>−/−</sup></i> HSPCs in a cleavage under targets and tagmentation assay. While <i>UHRF2</i> deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that <i>UHRF2</i> may play a role in the regulation of hematopoiesis.https://www.mdpi.com/2073-4425/14/8/1531<i>UHRF2</i>hematopoietic stem and progenitor cellshematopoiesis |
| spellingShingle | Takahiro Sano Koki Ueda Keiji Minakawa Tsutomu Mori Yuko Hashimoto Haruhiko Koseki Yasuchika Takeishi Kazuhiko Ikeda Takayuki Ikezoe Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice Genes <i>UHRF2</i> hematopoietic stem and progenitor cells hematopoiesis |
| title | Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice |
| title_full | Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice |
| title_fullStr | Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice |
| title_full_unstemmed | Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice |
| title_short | Impaired Repopulating Ability of <i>Uhrf2</i><sup>−/−</sup> Hematopoietic Progenitor Cells in Mice |
| title_sort | impaired repopulating ability of i uhrf2 i sup sup hematopoietic progenitor cells in mice |
| topic | <i>UHRF2</i> hematopoietic stem and progenitor cells hematopoiesis |
| url | https://www.mdpi.com/2073-4425/14/8/1531 |
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