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Series GSE155492 Query DataSets for GSE155492
Status Public on Mar 31, 2022
Title RNPS1 inhibits excessive TNF/TNFR signaling to support hematopoiesis in mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Null mutations of spliceosome components or cofactors are homozygous lethal in eukaryotes, but viable hypomorphic mutations provide an opportunity to understand the physiological impact of individual splicing proteins. We describe a viable missense allele of Rnps1, encoding an essential regulator of splicing and nonsense-mediated decay, identified in a mouse genetic screen for altered immune cell development. Homozygous mice displayed a stem cell-intrinsic defect in hematopoiesis of all lineages due to excessive apoptosis induced by TNF-dependent death signaling. Numerous splicing variants were observed in Rnps1 mutant splenic CD8+ T and HSC cells, potentially driven by dysregulated splicing, characterized by magnification of both intron retention and exon skipping. Strikingly, Tnf knockout rescued all hematopoietic cells to normal or near-normal levels in Rnps1 mutant mice. Thus, RNPS1 is necessary for accurate splicing, without which disinhibited TNF signaling triggers hematopoietic cell death.
 
Overall design Examination of transcript abundance and splicing variants in Rnps1+/+;Tnf+/+, Rnps1+/+;Tnf-/-, Rnps1F181I/F181I;Tnf+/+, or Rnps1F181I/F181I;Tnf-/- splenic CD8+ T and HSC cells
 
Contributor(s) Zhong X, Hildebrand SK
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jul 31, 2020
Last update date Mar 31, 2022
Contact name Sara K Hildebrand
E-mail(s) sara.hildebrand@utsouthwestern.edu, shilde9@gmail.com
Organization name UT Southwestern Medical Center
Department Center for the Genetics of Host Defense
Lab Beutler
Street address 5323 Harry Hines blvd
City Dallas
State/province TX
ZIP/Postal code 75390
Country USA
 
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (21)
GSM5242797 S43412
GSM5242798 S43103
GSM5242799 S43107
Relations
BioProject PRJNA649939
SRA SRP274576

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

Supplementary file Size Download File type/resource
GSE155492_Dataset_S1_gene_exp_diff_F181IF181I_WT__primary_CD8+_T_cells_.xlsx 53.3 Kb (ftp)(http) XLSX
GSE155492_Dataset_S2_Dataset_isoform_switches_with_consequence_primary_CD8_T_cells.xlsx 23.5 Kb (ftp)(http) XLSX
GSE155492_Dataset_S3_Dataset_isoform_switches_with_consequence_HSCs.xlsx 13.6 Kb (ftp)(http) XLSX
GSE155492_Dataset_S4_Dataset_splicing_F181IF181I_WT__primary_CD8+_T_cells_.xlsx 303.6 Kb (ftp)(http) XLSX
GSE155492_Dataset_S5_Dataset_splicing_F181IF181I_WT__HSCs_.xlsx 138.8 Kb (ftp)(http) XLSX
GSE155492_Dataset_S6_Dataset_splicing_F181IF181I_vs_F181IF181I_TNF_KO__primary_CD8+_T_cells_.xlsx 179.7 Kb (ftp)(http) XLSX
GSE155492_Dataset_S7_Dataset_splicing_F181IF181I_vs_F181IF181I_TNF_KO__HSCs_.xlsx 153.3 Kb (ftp)(http) XLSX
GSE155492_Dataset_S8_Dataset_splicing_F181I+_TNF_KO_vs_F181IF181I_TNF_KO__primary_CD8+_T_cells_.xlsx 84.3 Kb (ftp)(http) XLSX
GSE155492_Dataset_S9_Dataset_splicing_F181I+_TNF_KO_vs_F181IF181I_TNF_KO__HSCs_.xlsx 98.5 Kb (ftp)(http) XLSX
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Processed data are available on Series record

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