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Series GSE185982 Query DataSets for GSE185982
Status Public on Oct 15, 2021
Title Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis [cell line]
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 CAL1 BPDCN cells with shRNA knockdown of ZRSR2 or control shRNA at 0, 2, and 7 days after shRNA induction by doxycycline
 
Contributor(s) Lane AA
Citation(s) 34615655
Submission date Oct 15, 2021
Last update date Jan 14, 2022
Contact name Andrew Lane
E-mail(s) aalane@partners.org
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 (18)
GSM5628076 CAL1_CTRL_D0_1
GSM5628077 CAL1_CTRL_D0_2
GSM5628078 CAL1_CTRL_D0_3
This SubSeries is part of SuperSeries:
GSE185983 Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis
Relations
BioProject PRJNA771654
SRA SRP341591

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Supplementary file Size Download File type/resource
GSE185982_Togami_2_GEO_processed_data_file.xlsx 2.9 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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