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.
