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Series GSE61052 Query DataSets for GSE61052
Status Public on Mar 01, 2015
Title SRSF2 is essential for hematopoiesis and its myelodysplastic syndromes-related mutations dysregulate alternative pre-mRNA splicing
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary We report the biological function of Srsf2 in hematopoiesis in conditional knockout mouse models. Ablation of Srsf2 in the hematopoietic lineage caused embryonic lethality, and Srsf2-deficient fetal liver cells showed significantly enhanced apoptosis and decreased hematopoietic stem/progenitor cells. Induced ablation of Srsf2 in adult Mx1Cre/ Srsf2flox/flox mice upon polyinosinic:polycytidylic acid injection demonstrated a significant decrease in lineage-/Sca+/cKit+ cells in bone marrow. To reveal the functional impact of MDS-associated mutations in SRSF2, we profiled global splicing responses on an MDS-L cell line using RASL-seq, and found that the P95H missense mutation and P95 to R102 in-frame 8 amino-acid deletion caused significant changes in alternative splicing. The affected genes were enriched in cancer development and apoptosis. These findings suggest that intact Srsf2 is essential for the functional integrity of the hematopoietic system, and its mutations are likely key driver events to MDS.
Overall design MDS-L cells (in triplicate) were transfected by srsf2 shRNA only, or pTRIPZ vectors containing both srsf2 shRNA and srsf2 mutants cDNA including P95H and P95 8 amino acid deletion as well as wild-type construct, followed by Dox induction. Total RNAs were extracted and been analyzed by RASL-seq.
Contributor(s) Komeno Y, Qiu J, Zhou Y, Li H, Zhang D, Fu X
Citation(s) 26124281
Submission date Sep 03, 2014
Last update date May 15, 2019
Contact name Xiang-Dong Fu
Organization name UC San Diego
Department CMM
Lab George Palade Laboratories
Street address 9500 Gilman Drive, Room 231
City La Jolla
State/province CA
ZIP/Postal code 92093-0651
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (23)
GSM1495984 shRNA_only_Dox+_1
GSM1495985 shRNA_only_Dox+_2
GSM1495986 shRNA_only_Dox+_3
BioProject PRJNA260162
SRA SRP046267

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Supplementary file Size Download File type/resource
GSE61052_RAW.tar 2.5 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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