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本帖最后由 邓文龙 于 2021-11-21 12:03 编辑
Science:抗炎症是增强克隆造血功能的基础
对炎症的抵抗力是增强克隆造血功能的基础
领研网
2021/11/15
论文
论文标题:Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis
作者:S. Avagyan, J. E. Henninger, W. P. Mannherz, M. Mistry, J. Yoon, S. Yang, M. C. Weber, J. L. Moore, L. I. Zon
期刊:Science
发表时间:2021/11/05
数字识别码:10.1126/science.aba9304
摘要:Clonal hematopoiesis results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. We developed a technique that combines mosaic mutagenesis with color labeling of HSPCs to study how acquired mutations affect clonal fitness in a native environment. Mutations in clonal hematopoiesis–associated genes such as asxl1 promoted clonal dominance. Single-cell transcriptional analysis revealed that mutations stimulated expression of proinflammatory genes in mature myeloid cells and anti-inflammatory genes in progenitor cells of the mutant clone. Biallelic loss of one such immunomodulator, nr4a1, abrogated the ability of asxl1-mutant clones to establish clonal dominance. These results support a model where clonal fitness of mutant clones is driven by enhanced resistance to inflammatory signals from their mutant mature cell progeny.
所属学科:
生物
(导读 一晴)克隆造血由突变的造血干细胞和祖细胞(HSPC)为增强适应性而产生,但这种克隆如何扩展尚不清楚。本研究开发了一种结合了嵌合突变和HSPC颜色标记的技术,以研究获得性突变在自然环境中如何影响克隆适应性。克隆造血相关基因(如asxl1)的突变刺激了成熟髓系细胞中促炎基因的表达和突变克隆祖细胞中抗炎基因的表达,促进了克隆的优势地位。结果表明突变克隆的克隆适应性受到其突变成熟细胞子代对炎症信号增强的抗性驱动。
血液中的彩色克隆
血液等再生组织中的干细胞可以获得突变,从而获得生长优势,从而增加患癌症的机会。目前尚不清楚这种多样化的突变如何促进克隆适应性。阿瓦扬等人。在斑马鱼中生成了一个平台,用独特的色调标记克隆,同时诱导与人类血液疾病有关的基因突变。一些基因的突变导致克隆随着时间的推移而扩大,从而导致克隆优势。显性克隆中的祖细胞表达抗炎因子以抵抗其自身成熟后代产生的炎症环境,从而导致自我延续循环,促进克隆适应性。靶向这些抗性通路可用于减少克隆造血并预防其相关病理。——BAP
https://www.science.org/doi/10.1126/science.aba9304
https://www.linkresearcher.com/t ... 1-ad07-121d290522f0
克隆
https://zh.wikipedia.org/wiki/%E5%85%8B%E9%9A%86
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