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Series GSE239937 Query DataSets for GSE239937
Status Public on Feb 05, 2024
Title Smarca4 (Brg1) is a haploinsufficient B-cell tumor suppressor that fine-tunes centrocyte cell fate decisions [scMultiome]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary SMARCA4 encodes one of two mutually-exclusive ATPase subunits in the Brg/Brm associated factor (BAF) complex that is recruited by transcription factors to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ~30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency is able to cooperate with Myc over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of transcription factors that are activated in centrocytes to drive GC-exit, including SPI1, IRF4 and NFκB. Loss of activity for these factors drove aberrant Bcl6 activity within murine centrocytes and human BL cells. Smarca4 therefore facilitates chromatin accessibility for transcription factors that shape centrocyte trajectories, and loss of fine-control of these programs biases towards centroblast cell-fate and GC hyperplasia.
 
Overall design GC B cells were isolated from mice spleens at day 10 post-immunization using the Germinal Center B Cell (PNA) MicroBead Kit (Miltenyi Biotec,130-110-479), and sorted by FACS, followed by single-cell multiome analysis
 
Contributor(s) Green M
Citation(s) 38458188
Submission date Aug 02, 2023
Last update date May 07, 2024
Contact name Michael Green
E-mail(s) mgreen5@mdanderson.org
Phone 713-745-4244
Organization name The University of Texas MD Anderson Cancer Center
Department Department of Lymphoma/Myeloma
Street address 7455 Fannin Street
City Houston
State/province Texas
ZIP/Postal code 77054
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (16)
GSM7677859 WT, replicate 1, 10X multiome scATAC
GSM7677860 WT, replicate 1, 10X multiome scRNA
GSM7677861 WT, replicate 2, 10X multiome scATAC
This SubSeries is part of SuperSeries:
GSE254908 Smarca4 (Brg1) is a haploinsufficient B-cell tumor suppressor that fine-tunes centrocyte cell fate decisions
Relations
BioProject PRJNA1001513

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE239937_RAW.tar 8.2 Gb (http)(custom) TAR (of H5, TBI, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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