Blood:UTX通过调节衰老相关基因表达维持造血稳态

2020-12-01 Nebula-Qin MedSci原创

表观遗传调控对造血系统的维持至关重要,而表观遗传调控一旦失控就有可能导致造血系统紊乱。在该研究中,研究人员发现UTX通过全局调控衰老相关基因在造血系统中发挥重要作用。

表观遗传调控对造血系统的维持至关重要,而表观遗传调控一旦失控就有可能导致造血系统紊乱。

UTX(ubiquitously transcribed tetratricopeptide repeat, chromosome X),又称为KDM6A,是组蛋白H3(H3K27)上赖氨酸27的去甲基酶,也是Compass样和SWI/SNF复合体的组成部分。在该研究中,研究人员发现UTX通过全局调控衰老相关基因在造血系统中发挥重要作用

Utx基因缺陷(Utx-Δ/Δ)小鼠表现为骨髓偏斜伴发育不良、髓外造血、造血重建能力受损,并且对白血病的易感性增加,这些都是造血衰老的特征。

Utx-Δ/Δ小鼠的血细胞变化

RNA测序(RNA-seq)分析表明,Utx缺乏使年轻造血干/祖细胞(HSPC)的基因表达谱转换成了老年HSPC的基因表达谱Utx在HSC中的表达随着年龄的增长而降低;在Utx-Δ/Δ HSPC中,与衰老相关的标志物的表达增加、活性氧积累、DNA双链断裂修复受损

Utx-Δ/Δ和Utx-Δ/Uty小鼠的白血病分析

信号通路和染色质免疫沉淀(ChIP)分析结合RNA-seq数据表明,UTX主要通过去甲基酶依赖性和非依赖性表观遗传学编程维持随年龄的增长而下调的基因的表达,从而促进造血稳态。

值得注意的是,UtxΔ/ΔHSPC、衰老的肌肉干细胞、衰老的成纤维细胞和衰老的诱导神经细胞之间的通路变化有很大的重叠,这强烈表明不同组织的干细胞之间存在共同的衰老机制

原始出处:

Sera Yasuyuki,Nakata Yuichiro,Ueda Takeshi et al. UTX maintains functional integrity of murine hematopoietic system by globally regulating aging-associated genes.Blood, 2020. https://doi.org/10.1182/blood.2019001044

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    2020-12-30 mnda
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    2020-12-03 俅侠
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    2020-12-01 1211c54em14(暂无昵称)

    抗衰老,期待对抗方法

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