SIX1 and SIX4 double knockout transcriptome profiling in 2D cell lines derived from murine pancreatic tumors
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PROVIDER: PRJNA604776 | ENA |
REPOSITORIES: ENA
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Project description:Six1, Six4 and Myogenin are transcription factors that are known to be required for skeletal myogenesis. Currently, very little is known about the genes targeted by Six1 and Six4. Gene expression profiling when one or both transcription factors were knock-down by siRNA was performed to identify genes affected by their absence. We also hypothesized that Six1 and Six4 can work in cooperation with the myogenic regulatory factor (MRFs) family of transcription factors, such as Myogenin. Therefore, we performed the same type of experiment where the myogenin was knocked-down by siRNA to identify genes that are possibly regulated by the Six1 or Six4 in conjunction with Myogenin. C2C12 Myoblasts were transfected with siRNA against Six1, Six4, Six1 with Six4, Myogenin, or control 24h before start of differentiation. The cells were allowed to differentiate in differentiation medium for 24h and were harvested for gene expression profiling. Four replicates per siRNA were performed.
2010-07-30 | E-GEOD-19967 | biostudies-arrayexpress
Project description:Six1, Six4 and Myogenin are transcription factors that are known to be required for skeletal myogenesis. Currently, very little is known about the genes targeted by Six1 and Six4. Gene expression profiling when one or both transcription factors were knock-down by siRNA was performed to identify genes affected by their absence. We also hypothesized that Six1 and Six4 can work in cooperation with the myogenic regulatory factor (MRFs) family of transcription factors, such as Myogenin. Therefore, we performed the same type of experiment where the myogenin was knocked-down by siRNA to identify genes that are possibly regulated by the Six1 or Six4 in conjunction with Myogenin.
2010-07-05 | GSE19967 | GEO
Project description:Identification of the gene targets of the SIX transcription factors in myogenic stem cells and in whole back muscles during murine fetal development Pax7 expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the Sine oculis homeobox related Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior (TA) muscle. Mutant stem cells form hypotrophic myofibers that are not innervated but retain the ability to self-renew.
2020-10-07 | GSE159079 | GEO
Project description:Pancreatic ductal adenocarcinoma is aggressive disease with a dismal five-year survival of 5%. Gene expression profiling has been instrumental for subtype classification in cancer, highlighting fundamental differences in tumors at the molecular level. Over the last years, multiple genomics studies have led to the classification of PDAC into two major subtypes: classical and basal-type. The classical subtype expresses higher levels of endodermal lineage specifiers, including HNF4A, GATA6, FOXA2, FOXA3 than the basal-type. The basal-type confers a worse prognosis, raising the possibility that loss of these lineage specifiers might enhance the malignant potential of PDAC. We found that the lineage specifier HNF4a plays a key role in maintaining a transcriptional network that characterizes the classical subtype, restraining growth in different PDAC models. Additionally, we demonstrated that HNF4a controls PDAC cell identity and proliferation, and represses the expression of SIX family members, two mesodermal lineage specifiers highly expressed in basal-type.
2021-01-14 | GSE144750 | GEO
Project description:The aim of the experiment was to compare the transcriptome of Six1-/-Six4-/- and control embryos in order to identify genes under the control of Six proteins at E18.5. E18.5 RNAs from back muscles of three SixdKO and two control embryos were hybridized on Affymetrix mouse genome 430A2.0 arrays (Affymetrix, Strasbourg - France).
2009-10-08 | E-MEXP-1848 | biostudies-arrayexpress
Project description:Although an important association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago, an active role for the lymphatic system in metastatic dissemination has only recently been examined. We demonstrate that the Six1 homeoprotein promotes peri- and intra-tumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. We identify the pro-lymphangiogenic factor, VEGF-C, as required for this process, and demonstrate transcriptional induction as the mechanism of regulation of VEGF-C expression by Six1. Using a different, but complementary animal model, we show that while required, VEGF-C is not sufficient for the pro-metastatic effects of Six1. Verifying the clinical significance of this pro-metastatic Six1-VEGF-C axis, we demonstrate co-expression of Six1 and VEGF-C in human breast cancer. Two Control and two Six1 expressing MCF7 clones were orthotopically injected into NOD/Scid mice forming a total of 3 Control and 3 Six1 tumors that were allowed to grow to 2 cm^3 . The tumors were dissected and total RNA was isolated from each tumor and hybridized to Affymetrix arrays
2012-03-31 | E-GEOD-35314 | biostudies-arrayexpress
Project description:Although an important association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago, an active role for the lymphatic system in metastatic dissemination has only recently been examined. We demonstrate that the Six1 homeoprotein promotes peri- and intra-tumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. We identify the pro-lymphangiogenic factor, VEGF-C, as required for this process, and demonstrate transcriptional induction as the mechanism of regulation of VEGF-C expression by Six1. Using a different, but complementary animal model, we show that while required, VEGF-C is not sufficient for the pro-metastatic effects of Six1. Verifying the clinical significance of this pro-metastatic Six1-VEGF-C axis, we demonstrate co-expression of Six1 and VEGF-C in human breast cancer.
2012-04-01 | GSE35314 | GEO
Project description:The aim of the experiment was to compare the transcriptome of Six1-/-Six4-/- and control embryos in order to identify genes under the control of Six proteins at E10.5.<br><br>E10.5 embryos were eviscerated, head and limbs were discarded, the neural tube was removed, and RNAs were prepared with the remaining axial tissues. <br><br>E10.5 RNAs from three SixdKO and two control embryos were hybridized on Affymetrix mouse genome 430A2.0 arrays (Affymetrix, Strasbourg - France).
2009-10-08 | E-MEXP-1849 | biostudies-arrayexpress
Project description:Six1 is a developmental transcriptional regulator frequently overexpressed in human tumors. Recent results also show that SIX1 acts as a repressor of cell senescence, an antiproliferative response with key roles in tumor suppression, among other physiological and pathological settings. Here, we set to study the impact of SIX1 gain of function in transformation and tumorigenesis of fibroblasts, in connection with senescence. Using transcriptomic, histological, and functional analyses in murine cells and tumors of fibroblast origin, we show that SIX1 has a strong pro-tumorigenic action in this model, linked to the repression of a senescence-related gene signature and the activation of cellular plasticity, mediated at least in part by direct transcriptional regulation of the stemness factor Sox2. Moreover, functional analyses with human glioma cell lines also show that SIX1 controls SOX2 expression, senescence and self-renewal in this model. Collectively, our results support a general link of SIX1 with senescence and SOX2-mediated cell plasticity in tumors.
2019-02-12 | GSE113385 | GEO
Project description:Investigating genomic binding of SIX1 in A673 cells transduced with shSCR or one of two shSIX1 shRNAs to deplete SIX1.
2023-05-22 | GSE215350 | GEO