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| Status |
Public on Dec 02, 2021 |
| Title |
Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [II] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Clonal hematopoiesis (CH) results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. Here, 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 CH-associated genes, like 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.
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| Overall design |
To analyze the effect of germline runx1 homozygous mutant hematopoiesis compared to runx1 heterozygous hematopoiesis. Embryos from runx1 heterozygous incross were grown to adulthood. Whole kidney marrow cells from 4 runx1 heterozygous and 4 runx1 homozygous mutant zebrafish were collected for preparation for 10x single cell RNA sequencing.
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| Contributor(s) |
Avagyan S, Yang S, Zon LI |
| Citation(s) |
34735227 |
| |
| Submission date |
Jun 02, 2021 |
| Last update date |
Mar 03, 2022 |
| Contact name |
Leonard Zon |
| E-mail(s) |
zon@enders.tch.harvard.edu
|
| Organization name |
Boston Children's Hospital
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| Department |
Oncology/Hematology
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| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE176037 |
Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis |
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| Relations |
| BioProject |
PRJNA734619 |
| SRA |
SRP322388 |
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