A SOX9-B7x axis safeguards dedifferentiated tumor cells from immune surveillance to drive breast cancer progression [RNA-seq and ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE194201 | GEO | 2023/10/16
REPOSITORIES: GEO
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Project description:The transcription factor SOX9 can act as a pioneering factor in driving lineage dedifferentiation and tumor progression for breast cancer. To unbiasedly understand how committed luminal stem progenitor cells dedifferentiate into embryonic multipotent progenitor-like cells, we performed scRNA-seq in luminal cells FACS sorted from WT control mice and Sox9-GFP;C3-TAg mice at the age of 3.5 months when C3-TAg mice have developed extensive hyperplastic lesions but not yet malignant tumors.
2023-10-16 | GSE219109 | GEO
Project description:Human ß cell dedifferentiation as a potent mechanism of diabetes is gaining prominence. Several data suggest an upregulation of the transcription factor SOX9, a progenitor and duct cell marker during ß cell dedifferentiation. However, its targets in such cells need more understanding. Here, we overexpressed SOX9 and a constitutively active mutant (VP16-SOX9∆TAD) in Human pancreatic beta EndoC-ßH1 cells in order to understand its targets.
2018-01-31 | GSE104195 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-16 | GSE219110 | GEO
Project description:Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations, however the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG, and association with the Rela oncofusion in EPN. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.
2022-07-13 | PXD033863 | Pride
Project description:Lineage plasticity plays an important role in the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. Although studies suggest BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal and bipotent phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal/bipotent reprogramming remains unclear. Here we show that the transcription factor SOX9 acts as a determinant for ER– luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical NF-B signaling. Inactivation of p53 and Rb in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-bipotent reprogramming in vivo. SOX9 deletion inhibits the progression of benign, neoplastic lesions to invasive carcinoma. Furthermore, SOX9 is overexpressed and correlated with shorter relapse-free survival in human BLBC. These data show that ER– LSPC determinant SOX9 acts as a lineage-specific driver for BLBC transformation.
2020-06-09 | GSE135891 | GEO
Project description:Lineage plasticity plays an important role in the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. Although studies suggest BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal and bipotent phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal/bipotent reprogramming remains unclear. Here we show that the transcription factor SOX9 acts as a determinant for ER– luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical NF-KB signaling. Inactivation of p53 and Rb in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-bipotent reprogramming in vivo. SOX9 deletion inhibits the progression of benign, neoplastic lesions to invasive carcinoma. Furthermore, SOX9 is overexpressed and correlated with shorter relapse-free survival in human BLBC. These data show that ER– LSPC determinant SOX9 acts as a lineage-specific driver for BLBC transformation.
2020-06-09 | GSE135885 | GEO
Project description:The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, testes, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole mount in situ hybridization in wild-type and sox9 mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development. In each experiment, RNA was isolated from 48h wildtype and sox9a, sox9b double mutant embryos and the gene expression profiles were compared using microarrays. Three biological replicate experiments were performed, and each biological replicate contained a dyeswap.
2010-05-16 | E-GEOD-13482 | biostudies-arrayexpress
Project description:The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, testes, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole mount in situ hybridization in wild-type and sox9 mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development.
2008-11-08 | GSE13482 | GEO
Project description:Sox9 is an SRY-related transcription factor required for expression of cartilaginous matrix genes in the developing skeletal system and heart valve structures. In contrast to positively regulating formation of cartilaginous matrix, Sox9 has also been shown to negatively regulate matrix mineralization associated with bone formation. While the transcriptional activation of Sox9 target genes during chondrogenesis has been well studied, the mechanisms by which Sox9 represses osteogenic processs are not so clear. To address this, we performed a genome-wide Sox9 ChIP-on-chip approach using neonatal mouse lim tissue. Chromatin immunoprecipitation was performed with pooled Sox9 antibodies and normal rabbit IgG as control using neonatal mouse limb tissue. Samples include Sox9 IP and IgG IP.
2011-11-01 | E-GEOD-29058 | biostudies-arrayexpress
Project description:A major event in mammalian male sex determination is the induction of the testis determining factor Sry and its downstream gene Sox9. The current study provides one of the first genome wide analyses of the downstream gene binding targets for SRY and SOX9 to help elucidate the molecular control of Sertoli cell differentiation and testis development. A modified ChIP-Chip analysis using a comparative hybridization was used to identify 71 direct downstream binding targets for SRY and 109 binding targets for SOX9. Interestingly, only 5 gene targets overlapped between SRY and SOX9. In addition to the direct response element binding gene targets, a large number of atypical binding gene targets were identified for both SRY and SOX9. Bioinformatic analysis of the downstream binding targets identified gene networks and cellular pathways potentially involved in the induction of Sertoli cell differentiation and testis development. The specific DNA sequence binding site motifs for both SRY and SOX9 were identified. Observations provide insights into the molecular control of male gonadal sex determination. The current study provides one of the first genome wide analyses of the downstream gene binding targets for SRY and SOX9 to help elucidate the molecular control of Sertoli cell differentiation and testis development. At embryonic day 13 (E13) of pregnancy rats were euthanized and embryonic gonads were collected for chromatin. A modified ChIP-Chip analysis using a comparative hybridization was used to identify direct downstream binding targets for SRY and for SOX9. Then, bioinformatic analysis of the downstream binding targets was done to identify gene networks and cellular pathways that are potentially involved in the induction of Sertoli cell differentiation and testis development.
2014-12-05 | E-GEOD-63855 | biostudies-arrayexpress