TNFAIP3 Plays a Role in Aging of the Hematopoietic System.
TNFAIP3 Plays a Role in Aging of the Hematopoietic System.
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DOI：
10.3389/fimmu.2020.536442
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发表时间：
2020
影响因子：
7.3
通讯作者：
Starczynowski DT
中科院分区：
文献类型：
--
作者：
Smith MA;Culver-Cochran AE;Adelman ER;Rhyasen GW;Ma A;Figueroa ME;Starczynowski DT
造血干细胞和祖细胞(HSPC)在慢性炎症或衰老时会出现功能衰退。A20或TNFAIP3的单倍性不足，是一种天然免疫调节因子，与各种自身免疫性、炎症性和血液系统恶性肿瘤有关。根据先前对正常衰老过程中表观基因组和转录变化的分析，我们发现与年轻的HSPC相比，老年HSPC中A20的表达显著降低。在这里，我们表明，A20在年轻HSPC中的表达部分减少导致了衰老的特征。具体地说，造血细胞中A20的杂合缺失导致HSPC池扩大，HSPC适合性降低，并导致髓系偏向的造血。这些发现表明，A20在HSPC中的表达变化有助于HSPC的衰老表型，炎症状态和衰老之间可能存在一个共同的潜在机制，导致HSPC功能减弱。
Hematopoietic stem and progenitor cells (HSPC) experience a functional decline in response to chronic inflammation or aging. Haploinsufficiency of A20, or TNFAIP3, an innate immune regulator, is associated with a variety of autoimmune, inflammatory, and hematologic malignancies. Based on a prior analysis of epigenomic and transcriptomic changes during normal human aging, we find that the expression of A20 is significantly reduced in aged HSPC as compared to young HSPC. Here, we show that the partial reduction of A20 expression in young HSPC results in characteristic features of aging. Specifically, heterozygous deletion of A20 in hematopoietic cells resulted in expansion of the HSPC pool, reduced HSPC fitness, and myeloid-biased hematopoiesis. These findings suggest that altered expression of A20 in HSPC contributes to an aging-like phenotype, and that there may be a common underlying mechanism for diminished HSPC function between inflammatory states and aging.
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影响因子：
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作者：
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通讯作者：
Pasqualucci, Laura
影响因子：
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通讯作者：
Starczynowski DT