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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 07, 2023 |
| Title |
DARTseq identifies m6A targets in mouse primary cells |
| Organism |
Mus musculus |
| Experiment type |
Other
Expression profiling by high throughput sequencing
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| Summary |
The goal of this study is to identify m6A targets in mouse HSC and MPP1-4 cells
Stem cells regulate their self-renewal and differentiation fate outcomes through both symmetric and asymmetric divisions. When exposed to stress such as inflammation, stem cells can rapidly undergo symmetric commitment divisions to generate differentiated progenitors for tissue regeneration and immune maintenance. m6A RNA methylation controls symmetric commitment and inflammation of hematopoietic stem cells (HSCs) through unknown mechanisms. Here, we demonstrate that the nuclear speckle protein SON is an essential m6A target required for murine HSC self-renewal, symmetric commitment, and inflammation control. Global profiling of m6A identified that m6A mRNA methylation of Son increases during HSC commitment. Upon m6A depletion, Son mRNA increases, but its protein is depleted. Reintroduction of SON rescues defects in HSC symmetric commitment divisions and engraftment. Conversely, Son deletion results in a loss of HSC fitness, while overexpression of SON improves mouse and human HSC engraftment potential by increasing quiescence. Additionally, SON nuclear speckles asymmetrically and symmetrically segregate during HSC division, correlating with hematopoietic differentiation. Mechanistically, we found that SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program by indirectly reducing double-stranded RNAs and directly suppressing nascent transcription of proinflammatory chemokine CCL5. Depletion of CCL5 partially rescues the functional defect of m6A-deficient HSCs. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate.
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| Overall design |
Hanzhi,Luo
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| Contributor(s) |
Cortés-López M, Kharas MG |
| Citation(s) |
38065069 |
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| Submission date |
May 07, 2023 |
| Last update date |
Mar 07, 2024 |
| Contact name |
Michael G. Kharas |
| E-mail(s) |
[email protected]
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Molecular Pharmacology Program
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| Street address |
417 East 68th Street
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA968168 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE231862_DART-seq_mouse.featureCounts.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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