Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.
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| Title: | Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis. |
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| Authors: | Avagyan, S., Henninger, J. E., Mannherz, W. P., Mistry, M., Yoon, J., Yang, S., Weber, M. C., Moore, J. L., Zon, L. I. |
| Source: | Science (pre-March 2025). 11/5/2021, Vol. 374 Issue 6568, p768-772. 5p. 4 Graphs. |
| Subjects: | Hematopoiesis, Hematopoietic system, Cloning, Genes, Progenitor cells |
| Abstract: | 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 hematopoiesisÐassociated 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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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