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Series GSE184656 Query DataSets for GSE184656
Status Public on Sep 30, 2021
Title Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis [patients]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of plasmacytoid dendritic cells (pDCs). BPDCN occurs at least three times more frequently in men than women, but the reasons for this sex bias are unknown. Here, studying genomics of primary BPDCN and modeling disease-associated mutations, we link acquired alterations in RNA splicing to abnormal pDC development and inflammatory response through Toll-like receptors. Loss-of-function mutations in ZRSR2, an X chromosome gene encoding a splicing factor, are enriched in BPDCN and nearly all mutations occur in males. ZRSR2 mutation impairs pDC activation and apoptosis after inflammatory stimuli, associated with intron retention and inability to upregulate the transcription factor IRF7. In vivo, BPDCN-associated mutations promote pDC expansion and signatures of decreased activation. These data support a model in which male-biased mutations in hematopoietic progenitors alter pDC function and confer protection from apoptosis, which may impair immunity and predispose to leukemic transformation.
Overall design RNA sequencing of 11 BPDCNs and 4 normal pDC samples
Contributor(s) Lane AA
Citation(s) 34615655
Submission date Sep 23, 2021
Last update date Dec 30, 2021
Contact name Andrew Lane
Phone 617-632-4589
Organization name Dana-Farber Cancer Institute
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (15)
GSM5594628 Pt_1
GSM5594629 Pt_2
GSM5594630 Pt_3
This SubSeries is part of SuperSeries:
GSE185983 Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis
BioProject PRJNA765578
SRA SRP338394

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Supplementary file Size Download File type/resource
GSE184656_Togami_GEO_processed_data_file.xlsx 2.6 Mb (ftp)(http) XLSX
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Processed data are available on Series record

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