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Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.

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Title: Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.
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]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis.
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  Data: <searchLink fieldCode="AR" term="%22Avagyan%2C+S%2E%22">Avagyan, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Henninger%2C+J%2E+E%2E%22">Henninger, J. E.</searchLink><br /><searchLink fieldCode="AR" term="%22Mannherz%2C+W%2E+P%2E%22">Mannherz, W. P.</searchLink><br /><searchLink fieldCode="AR" term="%22Mistry%2C+M%2E%22">Mistry, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Yoon%2C+J%2E%22">Yoon, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+S%2E%22">Yang, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Weber%2C+M%2E+C%2E%22">Weber, M. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Moore%2C+J%2E+L%2E%22">Moore, J. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Zon%2C+L%2E+I%2E%22">Zon, L. I.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 11/5/2021, Vol. 374 Issue 6568, p768-772. 5p. 4 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Hematopoiesis%22">Hematopoiesis</searchLink><br /><searchLink fieldCode="DE" term="%22Hematopoietic+system%22">Hematopoietic system</searchLink><br /><searchLink fieldCode="DE" term="%22Cloning%22">Cloning</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Progenitor+cells%22">Progenitor cells</searchLink>
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  Data: 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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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: 11/5/2021
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