HyperTRIBE uncovers SYNCRIP RNA binding activity in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE202464 | GEO | 2023/03/01
REPOSITORIES: GEO
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Project description:HyperTRIBE uncovers SYNCRIP RNA binding activity in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)
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Project description:Transcriptional profiling of hematopoietic stem and progenitor cells comparing Bmi1 KO HSCs and MPPs to WT HSCs and MPPs
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Project description:Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)
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Project description:SYNCRIP, a member of the cellular heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA binding proteins, regulates various aspects of neuronal development and plasticity. Although SYNCRIP has been identified as a component of cytoplasmic RNA granules in dendrites of mammalian neurons, only little is known about the specific SYNCRIP target mRNAs that mediate its effect on neuronal morphogenesis and function. Here, we present a comprehensive characterization of the cytoplasmic SYNCRIP mRNA interactome using iCLIP in primary rat cortical neurons. We identify hundreds of bona fide SYNCRIP target mRNAs, many of which encode for proteins involved in neurogenesis, neuronal migration and neurite outgrowth. From our analysis, the stabilization of mRNAs encoding for components of the microtubule network, such as doublecortin (Dcx), emerges as a novel mechanism of SYNCRIP function in addition to the previously reported control of actin dynamics. Furthermore, we found that SYNCRIP interacts with miRISC and synergizes with pro-neural miRNAs, such as miR-9. Based on our findings, we propose a model whereby SYNCRIP promotes early neuronal differentiation by a two-tier mechanism involving the stabilization of pro-neural mRNAs by direct 3’UTR interaction and the repression of anti-neural mRNAs in a complex with neuronal miRISC. Together, our findings provide a rationale for future studies investigating the function of SYNCRIP in mammalian brain development and disease.
2021-05-05 | GSE149561 | GEO
Project description:Multipotent progenitors (MPP) and common dendritic cell progenitors (CDP) were obtained from mouse bone marrow, followed by in vitro culture with a specific cytokine cocktail and FACS sorting (Felker et al., 2010; Sere et al., 2012). Cells were treated with 10 ng/ml recombinant human TGF-b1 (R&D Systems, Minneapolis, USA) for 2, 4, 8, 12 and 24 h as described (Felker et al., 2010) or left untreated. Untreated multipotent progenitor (MPP) - MPP_0h_1 - MPP_0h_2 - MPP_0h_3 TGF-beta1 treated (2 hours) MPP - MPP_2h_1 - MPP_2h_2 - MPP_2h_3 TGF-beta1 treated (4 hours) MPP - MPP_4h_1 - MPP_4h_2 - MPP_4h_3 TGF-beta1 treated (8 hours) MPP - MPP_8h_1 - MPP_8h_2 - MPP_8h_3 TGF-beta1 treated (12 hours) MPP - MPP_12h_1 - MPP_12h_2 - MPP_12h_3 TGF-beta1 treated (24 hours) MPP - MPP_24h_1 - MPP_24h_2 - MPP_24h_3 Untreated common dendritic cell progenitor (CDP) - CDP_0h_1 - CDP_0h_2 - CDP_0h_3 TGF-beta1 treated (2 hours) CDP - CDP_2h_1 - CDP_2h_2 - CDP_2h_3 TGF-beta1 treated (4 hours) CDP - CDP_4h_1 - CDP_4h_2 - CDP_4h_3 TGF-beta1 treated (8 hours) CDP - CDP_8h_1 - CDP_8h_2 - CDP_8h_3 TGF-beta1 treated (12 hours) CDP - CDP_12h_1 - CDP_12h_2 - CDP_12h_3 TGF-beta1 treated (24 hours) CDP - CDP_24h_1 - CDP_24h_2 - CDP_24h_3
2014-04-15 | E-GEOD-46109 | biostudies-arrayexpress
Project description:RNA binding proteins (RBPs) tightly control mRNA abundance, stability and translation while mutations or altered expression of specific factors can drive malignancy1,2. However, the identity of the RBPs that govern cancer stem cell self-renewal remains poorly characterized. The MSI2 RBP is a central regulator of translation of the cancer stem cell program3-5,6. Here we report, through proteomics analysis of the MSI2 interacting RBP network and functional shRNA screening, 24 genes required for in vivo leukemia, 20 of which are direct MSI2 protein interactors. Seven of these shRNA screen hits were retested in vitro and found to be required for myeloid colony formation. SYNCRIP (also known as HNRP-Q or NSAP1) was the most differentially required gene between normal (c-kit enriched cells) and myeloid leukemia cells. SYNCRIP is highly expressed in mouse and human leukemia cells and its depletion increases apoptosis, differentiation and delays leukemogenesis. Gene expression profiling of SYNCRIP depleted cells demonstrates a loss of the MLL-AF9 and HOXA9 leukemia stem cell gene associated program. SYNCRIP interacts with MSI2 indirectly through shared mRNA targets (such as Hoxa9, Myc and Ikzf2) and MSI2 or HOXA9 overexpression rescues the effects of SYNCRIP depletion. Strikingly, the shRNA-SYNCRIP gene expression signature can predict survival in AML patients. Overall, we uncovered a functionally dysregulated riboproteome in cancer that can be further distinguished from normal cells and propose that targeting this network could result in a novel therapeutic strategy in eradicating cancer stem cells.
2017-04-24 | GSE74178 | GEO
Project description:SYNCRIP depletion results in HSCs losing their self renewal abilities. Single cell sequencing was conducted in SYNCRIP WT and KO bone marrow LK (lineage -, cKit+) cells to decipher the effect of Syncrip deletion on cellular identities along the hematopoietic hierarchy, and to gain an in-depth assessment of the transcriptomic changes in different cell types upon SYNCRIP loss.
2023-03-01 | GSE202421 | GEO
Project description:Alterations in SYNCRIP activity were found to alter gene transcription in leukemia cells. The effects of transcription alterations on expression of the corresponding proteins were investigated by LC/MSMS
2023-05-10 | PXD019779 | Pride
Project description:We showed that in response to chemotherapy, dying cancer cells can secrete spliceosomal components into the extracellular space. These therapy-induced secretomes enriched with spliceosomal components promote the chemoresistance of recipient tumor cells. We demonstrated that spliceosomal proteins SNU13 and SYNCRIP can relocalize from dying tumor cells to recipient tumor cells via extracellular vesicles. To investigate whether the increased abundance of splicing factors could be the reason for the acquisition of a more aggressive phenotype by tumor cells, we got SKOV3 cell lines stably overexpressing SYNCRIP or SNU13. These cell lines were more resistant to cisplatin compared to control cell line expressing empty vector. Next, to investigate how the therapy response is formed in tumor cells with and without overexpression of spliceosomal proteins SNU13 or SYNCRIP, we performed RNAseq analysis of these cells before and 24 hours after cisplatin treatment. Enrichement analyses showed that in response to cisplatin, genes associated with DNA repair and cell cycle regulation were upregulated in cancer cell lines overexpressing SYNCRIP or SNU13 compared with control cells. This study revealed previously unknown signaling molecules in the microenvironment of ovarian cancer that have potential clinical significance.
2024-04-24 | GSE241913 | GEO
Project description:An investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis. This data compliments the miniChIP-chip data obtained from the same cell types as described in Weishaupt et al., 2009 (Blood). An Affymetrix genechip study using total RNA recovered from three separate FACS isolated HSC and MPP samples. The HSC and MPP gene expression data was analyzed alongside the PreMegEs and CD4+ T cells datasets obtained from our previous work (Pronk et al., 2007, Rolf et al. 2008). HSCs are phenotypically identified in bone marrow as lineage-, cKit+, Sca1+, CD150+, Flk2/Flt3- (LSKCD150+ cells). MPPs are phenotypically identified in bone marrow as lineage-, cKit+, Sca1+, CD150-, Flk2/Flt3+ (LSKCD150- cells). PreMegEs are phenotypically identified in bone marrow as lineage-, cKit+, Sca1-, CD150+, CD105- and CD41- as described in Pronk et al., 2007. Splenic-derived CD4+ T cells are phentypically identified as CD4+, CD8-, B220-, Nk1.1- cells as described in Rolf et al., 2008.
2009-11-09 | E-GEOD-18669 | biostudies-arrayexpress