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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 [RNA-seq2] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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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 |
RNAseq of Lin-/cKit+/eYFP+ (Immature haematopoietic multipotent progenitors) sorted from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 P95H generated by deep sequencing, using Illumina X-ten.
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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 |
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Submission date |
Oct 14, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Alistair Morgan Chalk |
E-mail(s) |
achalk@svi.edu.au, alistair.chalk@gmail.com
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Organization name |
St Vincent's Institute of Medical Research
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Department |
Stem Cell Regulation Unit
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Lab |
Walkley
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Street address |
9 Princes st, Fitzroy
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City |
Melbourne |
State/province |
VIC |
ZIP/Postal code |
3065 |
Country |
Australia |
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Platforms (1) |
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Samples (6)
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GSM2811301 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 +/+_1 |
GSM2811302 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 +/+_2 |
GSM2811303 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 +/+_3 |
GSM2811304 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 P95H/+_1 |
GSM2811305 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 P95H/+_2 |
GSM2811306 |
Lin-/cKit+/eYFP+ cells from whole bone marrow in vivo tamoxifen treated hScl-CreERT R26eYFP Srsf2 P95H/+_3 |
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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. |
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Relations |
BioProject |
PRJNA414292 |
SRA |
SRP119954 |