|
| Status |
Public on Jun 18, 2018 |
| Title |
Physiologic expression of Srsf2(P95H) causes myeloid expansion, impaired competitive stem cell function and initiates the myeloproliferative/myelodysplastic syndrome in vivo [WES] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Mutations in the RNA splicing complex member SRSF2 are found frequently in myelodysplastic syndrome and related malignancies such as chronic myelomonocytic leukemia. These mutations cluster on proline 95, with P95H the most frequent. How SRSF2P95H mutations modify hematopoiesis and promote MDS/MPN development is not clear. We have established a conditionally activatable Srsf2P95H/+ knock-in allele which, when expressed within the hematopoietic stem cell populations caused profound myeloid bias, at the expense of erythroid and lymphoid cells, and a reduced frequency and competitive repopulation of HSCs. Long-term aging of Srsf2P95H/+ resulted in the development of MDS/MPN characterised by myeloid dysplasia and monocytosis. Reproducible key phenotypic features make this a mouse model suitable for mechanistic and preclinical MDS sudies.
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| Overall design |
Whole Exome Sequencing of in vivo tamoxifen treated R26CreERT2 Srsf2 P95H, using Illumina HiSeq X Ten. Exome sequencing data was acquired for 6 samples from 50-60 weeks post tamoxifen treatment (time of euthanasia due to animals becoming moribund). Genomic DNA was isolated from both whole BM and matched ear tissue from three independent animals (two R26-CreERT2 Srsf2P95H/+ and one hScl-CreERT R26eYFP Srsf2P95H/+ ). SRA Study accession: SRP108226.
Please note that, for somatic mutation calling, each processed data file was generated from two samples. For the variant calling, there are multiple files per animal+ tissue depending on the method used.
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| Contributor(s) |
Walkley CR, Smeets MF, Tan SY, Xu J, Anande G, Unnikrishnan A, Chalk AM, Pimanda JE, Wall M, Purton LE |
| Citation(s) |
29903888 |
| |
| Submission date |
Jun 09, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Alistair Morgan Chalk |
| E-mail(s) |
achalk@svi.edu.au, alistair.chalk@gmail.com
|
| Organization name |
St Vincent's Institute of Medical Research
|
| Department |
Stem Cell Regulation Unit
|
| Lab |
Walkley
|
| Street address |
9 Princes st, Fitzroy
|
| City |
Melbourne |
| State/province |
VIC |
| ZIP/Postal code |
3065 |
| Country |
Australia |
| |
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| Platforms (1) |
|
| Samples (6)
|
| GSM2655966 |
Whole Bone Marrow in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 108 |
| GSM2655967 |
Ear in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 108 |
| GSM2655968 |
Whole Bone Marrow in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 136 |
| GSM2655969 |
Ear in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 136 |
| GSM2655970 |
Whole Bone Marrow in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 54 |
| GSM2655971 |
Ear in vivo tamoxifen treated R26CreERT2 Srsf2 P95H from animal 54 |
|
| This SubSeries is part of SuperSeries: |
| GSE99852 |
Physiologic expression of Srsf2(P95H) causes myeloid expansion, impaired competitive stem cell function and initiates the myeloproliferative/myelodysplastic syndrome in vivo. |
|
| Relations |
| SRA |
SRP108226 |
| BioProject |
PRJNA389794 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99850_RAW.tar |
36.8 Mb |
(http)(custom) |
TAR (of TXT, VCF) |
| GSE99850_SVI_SRSF2_108_Somatic_mutation_detection_Stelka_Passed_Somatic_Indels.vcf.gz |
4.5 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_108_Somatic_mutation_detection_Stelka_Passed_Somatic_SNPs.vcf.gz |
40.9 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_108_Somatic_mutation_detection_VarScan2_Filtered_Somatic_Indels.txt.gz |
9.9 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_108_Somatic_mutation_detection_VarScan2_Filtered_Somatic_SNPs.txt.gz |
48.3 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_108_Somatic_variants_VarScan2_Filtered_Somatic_Indels_SnpEff_Annotated.txt.gz |
24.8 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_108_Somatic_variants_VarScan2_Filtered_Somatic_SNPs_SnpEff_Annotated.txt.gz |
93.5 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_108_Somatic_variants_strelka_Passed_Somatic_Indels_SnpEff_Annotated.txt.gz |
8.3 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_108_Somatic_variants_strelka_Passed_Somatic_SNPs_SnpEff_Annotated.txt.gz |
152.4 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_mutation_detection_Stelka_Passed_Somatic_Indels.vcf.gz |
4.8 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_136_Somatic_mutation_detection_Stelka_Passed_Somatic_SNPs.vcf.gz |
54.9 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_136_Somatic_mutation_detection_VarScan2_Filtered_Somatic_Indels.txt.gz |
3.8 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_mutation_detection_VarScan2_Filtered_Somatic_SNPs.txt.gz |
16.3 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_variants_VarScan2_Filtered_Somatic_Indels_SnpEff_Annotated.txt.gz |
9.3 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_variants_VarScan2_Filtered_Somatic_SNPs_SnpEff_Annotated.txt.gz |
35.2 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_variants_strelka_Passed_Somatic_Indels_SnpEff_Annotated.txt.gz |
9.1 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_136_Somatic_variants_strelka_Passed_Somatic_SNPs_SnpEff_Annotated.txt.gz |
210.3 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_mutation_detection_Stelka_Passed_Somatic_Indels.vcf.gz |
5.9 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_54_Somatic_mutation_detection_Stelka_Passed_Somatic_SNPs.vcf.gz |
77.6 Kb |
(ftp)(http) |
VCF |
| GSE99850_SVI_SRSF2_54_Somatic_mutation_detection_VarScan2_Filtered_Somatic_Indels.txt.gz |
8.8 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_mutation_detection_VarScan2_Filtered_Somatic_SNPs.txt.gz |
32.4 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_variants_VarScan2_Filtered_Somatic_Indels_SnpEff_Annotated.txt.gz |
22.2 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_variants_VarScan2_Filtered_Somatic_SNPs_SnpEff_Annotated.txt.gz |
59.0 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_variants_strelka_Passed_Somatic_Indels_SnpEff_Annotated.txt.gz |
10.9 Kb |
(ftp)(http) |
TXT |
| GSE99850_SVI_SRSF2_54_Somatic_variants_strelka_Passed_Somatic_SNPs_SnpEff_Annotated.txt.gz |
292.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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