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Series GSE242069 Query DataSets for GSE242069
Status Public on Apr 24, 2024
Title Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, and thereby germinal center and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. The comparative analysis of RNA-seq data from B cells and another 8 hnRNPL-depleted cell types reveals a common function in the Myc and E2F transcriptional programs required for proliferation, likely borne out of a large alternative splicing change affecting multiple transcription regulators. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like SIRT1, KDM6A, and NSD2, were conserved across cell types, which could contribute to gene expression changes upon hnRNPL loss. SIRT1 reduction due to alternative splicing, and other transcriptional changes suggested mitochondrial defects in hnRNPL-deficient B cells. We confirmed dysfunctional mitochondria and ROS overproduction, which could explain the B cell activation defect. Thus, hnRNPL is essential for the resting to activated B cell transition by regulating transcriptional programs, most likely by splicing regulation affecting several histone modifiers.
 
Overall design To investigate gene expression and splicing changes upon hnRNPL depletion in activated B cells, CD21-cre mice were crossed with hnRNPL F/F mice.
We then perform paired-end RNA-seq of hnRNPL F/F CD21-cre and CD21-cre (control) splenic B cells, stimulated with LPS+IL4 for 24h.
Differential gene expression for WT vs hnRNPL-deficient activated B cells. Normalized counts, log2 fold changes and DESeq2 padj values are in the supplementary file "norm_counts.txt".
Web link https://doi.org/10.1038/s44319-024-00152-3
 
Contributor(s) Subramani P, Fraszczak J, Helness A, Estall JL, Möröy T, Di Noia JM
Citation(s) 38744970
Submission date Aug 31, 2023
Last update date Jul 24, 2024
Contact name Javier M Di Noia
E-mail(s) javier.di.noia@ircm.qc.ca
Phone 514-987-5642
Organization name Institut de recherches cliniques de Montréal (IRCM)
Lab Molecular biology of the B cell Research Unit
Street address 110 Pine Avenue West
City Montréal
State/province QC
ZIP/Postal code H2R1W7
Country Canada
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7748488 WT rep1
GSM7748489 WT rep2
GSM7748490 WT rep3
Relations
BioProject PRJNA1011292

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
GSE242069_RAW.tar 1.5 Gb (http)(custom) TAR (of BW)
GSE242069_normCounts.txt.gz 2.8 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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