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| Status |
Public on Feb 02, 2024 |
| Title |
ARID1A Orchestrates SWI/SNF-mediated Sequential Binding of Transcription Factors and Its Deficiency Drives Pre-memory B-cell Fate and Lymphomagenesis [Arid1a_multiome] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. Our study shows that ARID1A orchestrates B-cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling. The absence of ARID1A tilts GC cell-fate towards immature IgM+CD80-PDL2- memory B-cells, known for their potential to re-enter new GCs. When combined with BCL2 oncogene, ARID1A haploinsufficiency hastens the progression of aggressive follicular lymphomas in mice. Remarkably, follicular lymphoma patients with ARID1A-inactivating mutations preferentially display an immature memory B-cell-like state with increased transformation risk to aggressive disease. These observations offer mechanistic understanding into the emergence of both indolent and aggressive lymphomas in ARID1A-mutant patients through formation of immature memory-like clonal precursors. Lastly, we demonstrate that ARID1A mutation induces synthetic lethality to SMARCA2/4 inhibition, paving the way for potential precision therapy for high-risk patients.
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| Overall design |
GC cells from splenocytes were sorted and underwent the manufacturer's nuclei preparation procedure. Then, about 20,000 nuclei were placed into a 10x Chromium X instrument. The remainder of the library preparation steps were conducted in accordance with the manufacturer's protocol
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| Contributor(s) |
Chin CR, Barisic D, Meydan C, Teater M |
| Citation(s) |
38458187 |
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| Submission date |
Jul 21, 2023 |
| Last update date |
May 03, 2024 |
| Contact name |
Christopher Russell Chin |
| E-mail(s) |
chc2077@med.cornell.edu
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| Phone |
3393640514
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| Organization name |
Weill Cornell
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| Lab |
Melnick Lab
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| Street address |
413 E 69th Street, Belfer Building, BB-1462
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| City |
New York City |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (14)
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| GSM7657351 |
Arid1aHet-2, scATAC-seq |
| GSM7657352 |
Arid1aHom-2, scATAC-seq |
| GSM7657353 |
WT-2, scATAC-seq |
| GSM7657354 |
WT-3, scATAC-seq |
| GSM7657355 |
WT-1, scRNA-seq |
| GSM7657356 |
Arid1aHom-1, scRNA-seq |
| GSM7657357 |
Arid1aHet-1, scRNA-seq |
| GSM7657358 |
Arid1aHet-2, scRNA-seq |
| GSM7657359 |
Arid1aHom-2, scRNA-seq |
| GSM7657360 |
WT-2, scRNA-seq |
| GSM7657361 |
WT-3, scRNA-seq |
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| This SubSeries is part of SuperSeries: |
| GSE237990 |
ARID1A Orchestrates SWI/SNF-mediated Sequential Binding of Transcription Factors with ARID1A Loss Driving Pre-memory B Cell Fate and Lymphomagenesis |
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| Relations |
| BioProject |
PRJNA997347 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237987_RAW.tar |
7.7 Gb |
(http)(custom) |
TAR (of TBI, TSV) |
| GSE237987_arid1a.csm.broad.hrna.sl.rds.gz |
7.8 Mb |
(ftp)(http) |
RDS |
| GSE237987_final.arid1a.msobj.pseudotime.rds.gz |
6.7 Gb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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