The transcription factor Stat-1 is essential for Schwann cell differentiation, myelination and myelin sheath regeneration [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE211337 | GEO | 2023/09/11
REPOSITORIES: GEO
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Project description:To investigate the potential mechanisms of Stat1 regulation of Schwann cell (SC) differentiation, we performed a RNA sequencing (RNA-seq) of SCs grown under differentiation conditions treated with Stat1-siRNA or with non-targeting negative control siRNA (Scramble).
2023-09-11 | GSE211336 | GEO
Project description:BackgroundMyelin sheath is a crucial accessory to the functional nerve-fiber unit, its disruption or loss can lead to axonal degeneration and subsequent neurodegenerative diseases (NDs). Notwithstanding of substantial progress in possible molecular mechanisms underlying myelination, there is no therapeutics that prevent demyelination in NDs. Therefore, it is crucial to seek for potential intervention targets. Here, we focused on the transcriptional factor, signal transducer and activator of transcription 1 (Stat1), to explore its effects on myelination and its potential as a drug target.MethodsBy analyzing the transcriptome data obtained from Schwann cells (SCs) at different stages of myelination, it was found that Stat1 might be involved in myelination. To test this, we used the following experiments: (1) In vivo, the effect of Stat1 on remyelination was observed in an in vivo myelination mode with Stat1 knockdown in sciatic nerves or specific knockdown in SCs. (2) In vitro, the RNA interference combined with cell proliferation assay, scratch assay, SC aggregate sphere migration assay, and a SC differentiation model, were used to assess the effects of Stat1 on SC proliferation, migration and differentiation. Chromatin immunoprecipitation sequencing (ChIP-Seq), RNA-Seq, ChIP-qPCR and luciferase activity reporter assay were performed to investigate the possible mechanisms of Stat1 regulating myelination.ResultsStat1 is important for myelination. Stat1 knockdown in nerve or in SCs reduces the axonal remyelination in the injured sciatic nerve of rats. Deletion of Stat1 in SCs blocks SC differentiation thereby inhibiting the myelination program. Stat1 interacts with the promoter of Rab11-family interacting protein 1 (Rab11fip1) to initiate SC differentiation.ConclusionOur findings demonstrate that Stat1 regulates SC differentiation to control myelinogenic programs and repair, uncover a novel function of Stat1, providing a candidate molecule for clinical intervention in demyelinating diseases.
| S-EPMC10291779 | biostudies-literature
Project description:To obtain the dynamic gene expression of myelinating Schwann cells, we have employed gene expression profiling microarray as a discovery platform to analyze the gene expression of Schwann cells in different stages of myelination in an DRG neuron and SC co-culture myelinating model. Rat Schwann cells and dorsal root ganglion (DRG) neurons were cocultured and induced myelination in DMEM medium containing 15% FBS, 50 ng/ml NGF and 50 μg/ml L-ascorbic acid for 21d. During the co-cultivation, myelinating SCs at different stages dissected by Laser microdissection (LMD) in myelination model (i.e. co-culture 1d, 3d, 7d, 14d, 21d), the Schwann cells without co-culture as control samples (i.e. co-culture 0d). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of DRG/SC co-culture 21 days. The 3 phases were designated as “premyelination”, “myelination”, and “mature phase”, respectively, by referring to morphological observation of post co-culture changes and gene ontology (GO) analysis.
2022-09-21 | GSE163132 | GEO
Project description:The remarkable plasticity of Schwann cells (SCs) is essential for nerve regeneration but also contributes to neuropathies and cancer progression. It has not yet been investigated whether the adaptive potential of SCs is manifested in stromal, tumor associated SCs characteristically found within a benign subtype of neuroblastic tumors (NBTs). We here performed transcriptome profiling of human NBTs, rich and poor in SC stroma, as well as human injured nerves, rich in repair SCs, revealing that stromal SCs exhibit a repair SC characteristic gene expression signature. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on NBT cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of aggressive NBT cells. EGFL8 expression further correlated with favorable tumor stage and increased patient survival. Our findings suggest that stromal SCs exert nerve repair associated functions in the tumor-environment and underline the therapeutic value of SC-derived factors for aggressive, SC stroma-poor NBTs.
2021-01-13 | PXD018267 | Pride
Project description:The remarkable plasticity of Schwann cells (SCs) is essential for nerve regeneration but also contributes to neuropathies and cancer progression. It has not yet been investigated whether the adaptive potential of SCs is manifested in stromal, tumor associated SCs characteristically found within a benign subtype of neuroblastic tumors (NBTs). We here performed transcriptome profiling of human NBTs, rich and poor in SC stroma, as well as human injured nerves, rich in repair SCs, revealing that stromal SCs exhibit a repair SC characteristic gene expression signature. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on NBT cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of aggressive NBT cells. EGFL8 expression further correlated with favorable tumor stage and increased patient survival. Our findings suggest that stromal SCs exert nerve repair associated functions in the tumor-environment and underline the therapeutic value of SC-derived factors for aggressive, SC stroma-poor NBTs.
2021-01-04 | PXD022217 | Pride
Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage derived sarcomas with poor prognosis. The molecular events underlying SC lineage cells-to-MPNST transformation remain elusive. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyper-proliferation. Conversely, disruption of TAZ/YAP activity alleviates tumor burden in Lats1/2-deficient mice and inhibits human MPNST cell proliferation. Moreover, genome-wide target profiling reveals that TAZ/YAP-TEAD1 directly activates a set of oncogenic programs in SCs including PDGFR/RAF signaling. Co-targeting TAZ/YAP and PDGFR/RAF signaling efficaciously reduces tumorigenicity in Lats1/2-deficient tumors. Thus, our findings establish a previously unrecognized convergence between LATS1/2-TAZ/YAP pathway and MPNST pathogenesis, suggesting that combined inhibition of TAZ/YAP-PDGFR/RAF signaling may be beneficial in MPNSTs.
2018-02-13 | GSE99040 | GEO
Project description:The remarkable plasticity of Schwann cells (SCs) is essential for nerve regeneration but also contributes to neuropathies and cancer progression. It has not yet been investigated whether the adaptive potential of SCs is manifested in stromal, tumor associated SCs characteristically found within a benign subtype of neuroblastic tumors (NBTs). We here performed transcriptome profiling of human NBTs, rich and poor in SC stroma, as well as human injured nerves, rich in repair SCs, revealing that stromal SCs exhibit a repair SC characteristic gene expression signature. In turn, primary repair SCs had a pro-differentiating and anti-proliferative effect on NBT cell lines after direct and trans-well co-culture. Within the pool of secreted stromal/repair SC factors, we identified EGFL8, a matricellular protein with so far undescribed function, to induce neuronal differentiation of aggressive NBT cells. EGFL8 expression further correlated with favorable tumor stage and increased patient survival. Our findings suggest that stromal SCs exert nerve repair associated functions in the tumor-environment and underline the therapeutic value of SC-derived factors for aggressive, SC stroma-poor NBTs.
2020-12-23 | GSE147635 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-09-11 | GSE211338 | GEO
Project description:Background: Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Methods: Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. Additionally, miRNA sequencing was performed on induced ADSCs, followed by bioinformatic analysis and validation of the results. Results: SC-Exos were taken up by human ADSCs. The RNA and protein expression levels of S100, NGFR, MPZ and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, despite no significant difference to the Dezawa’s method group, which was also consistent with the immunofluorescence results. According to the sequencing results, there were a total of 72 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 6 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Conclusions: Our data suggest that SC-Exos are able to induce the differentiation of ADSCs into SCs in vitro. It is speculated that the differentially expressed miRNAs play a significant role in the differentiation process.
2022-02-13 | GSE183623 | GEO
Project description:Elucidating the genes regulated during cell-cell communication remains fascinating considering the importance of cell recognition and downstream signaling through development and in many diseases. In the peripheral nervous system, the interaction between Schwann cells (SCs) and axons is crucial as it allows their survival and induces SCs to differentiate and engage a process of myelination. To get further insight the molecular mechanisms resulting from this cell interaction, comparative gene analysis between SCs and SCs co-cultured with DRG neurons were performed and led us to identify a set of 32 genes regulated in SCs in the early stage of neuron-SC contact. Expression of several candidates were analyzed by QPCR during development and we demonstrate using a blocking antibody approach in an in vitro myelination assay that one candidate was not only upregulated in response to axonal contact but also controls peripheral myelination. Three biological replicates each in dye swap for 22k slides and two biological replicates each in dye swap for NeuroDev2
2011-01-15 | E-GEOD-17366 | biostudies-arrayexpress