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β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [CUT&RUN]

GSE249199 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/02/29 Platform GPL24247
Summary
Replication stress is a main driver of functional decline of hematopoietic stem cells (HSCs), which carry the highest burden of maintaining genomic integrity and functionality within the hematopoietic system. Here, we identify a novel signaling axis in which β-catenin and Hoxa9 function in a compensatory manner to preserve HSC functionality by protecting DNA replication dynamics and genomic integrity, in part via regulation of Prmt1 activity. Co-inactivation of β-catenin and Hoxa9 induces severe hematopoietic defects accompanied by accumulating replication stress and DNA damage resulting in functional HSC decline. Furthermore, we illustrate how β-catenin and Hoxa9 pathways converge on the pivotal downstream target, Prmt1, which functions to maintain an adequate supply of DNA replication and repair factors. Prmt1 aids in alleviating replication stress and DNA damage accumulation thereby preserving HSC integrity and functionality.
Published in
Hematopoietic stem cell quiescence and DNA replication dynamics maintained by the resilient β-catenin/Hoxa9/Prmt1 axis
Lynch J, Troadec E, Fung TK et al. · Blood 2024 · PMID 38211335 · doi:10.1182/blood.2023022082
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Also filed as BioProject PRJNA1047656 and SRA study SRP475401. Searching any of these in the dataset finder brings you back here.

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