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在小鼠中Uhrf2^-/-血造原始细胞的再生能力受损

Takahiro Sano¹, Koki Ueda², Keiji Minakawa²

¹Department of Hematology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.

|August 26, 2023

概括

删除UHRF2 (与PHD和RING指域2类似的ubiquitin) 会影响造血干细胞/原生细胞的功能. 在UHRF2淘汰的小鼠中,重新繁殖能力有所降低,这表明UHRF2调节了血液形成.

科学领域:

* 分子生物学 * 分子生物学
* 遗传学遗传学是一门学科
* 血液学血液学

背景情况:

* UHRF蛋白通过无处不在调节基因表达.
* 在急性白血病中观察到减少UHRF2表达.
* UHRF2在血液形成中的特定作用目前尚不清楚.

研究的目的:

* 为了研究UHRF2在血液形成中的功能.
* 确定UHRF2删除对血液细胞发育和干细胞功能的影响.

主要方法:

* 产生和分析Uhrf2淘汰赛小鼠.
*使用骨髓移植 (BMT) 的竞争性重新定位测试.
*RNA测序和CUT&Tag对造血干细胞/原生细胞 (HSPC) 的测定.

主要成果:

* Uhrf2 淘汰赛小鼠表现出正常的血细胞计数和骨髓形态.
*竞争性重新填充试验显示,在BMT之后的所有血统中,Uhrf2细胞的比例下降.
*RNA测序表明 Uhrf2 HSPC 中干细胞功能基因的下调,H3K9 三甲基化增加.

结论:

* UHRF2 缺失会损害造血干细胞/原始细胞的再生能力.
*UHRF2在血液形成中起着调节作用,可能通过表观遗传机制.
* UHRF2 删除没有诱导血液恶性瘤或为HSPCs提供增长优势.

关键词:

在 UHRF2 的情况下,UHRF2 血液形成血液形成造血干细胞和原始细胞.

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