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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 29, 2024 |
| Title |
β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner [CUT&RUN] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| Overall design |
CUT&RUN was performed using 0.5 million HSPCs from WT BL6 mice or Ctnnb1-Biotin-3xFLAG knockin mice (JAX:029511) according to Epicypher CUT&RUN Protocol V2.0.
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| Contributor(s) |
Lynch J, Troadec E, Fung TK, Gladysz K, Virely C, Lau P, Cheung N, Zeisig B, Wong JW, Lopes M, Huang S, So CW |
| Citation(s) |
38211335 |
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| Submission date |
Dec 01, 2023 |
| Last update date |
Jun 06, 2024 |
| Contact name |
Eric So |
| E-mail(s) |
eric.so@kcl.ac.uk
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| Organization name |
KCL
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| Lab |
So Lab
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| Street address |
School of Cancer and Pharmaceutical Sciences
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| City |
London |
| ZIP/Postal code |
SE5 9NU |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| GSM7928231 |
ckit+WT ms BM, IgG, replicate 1, CUT&RUN |
| GSM7928232 |
ckit+ WT ms BM, IgG, replicate 2, CUT&RUN |
| GSM7928233 |
ckit+ WT ms BM, HOXA9, replicate 1, CUT&RUN |
| GSM7928234 |
ckit+ WT ms BM, HOXA9, replicate 2, CUT&RUN |
| GSM7928235 |
CTNB ckit+ BM, IgG, replicate 1, CUT&RUN |
| GSM7928236 |
CTNB ckit+ BM, FLAG, replicate 1, CUT&RUN |
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| This SubSeries is part of SuperSeries: |
| GSE235821 |
β-catenin and Hoxa9 preserve DNA replication dynamics, genomic integrity and stem cell functionality in a Prmt1-dependent manner |
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| Relations |
| BioProject |
PRJNA1047656 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249199_RAW.tar |
800.0 Kb |
(http)(custom) |
TAR (of NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
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