Sox10 is required for systemic initiation of bone mineralization
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PROVIDER: PRJNA1191617 | ENA |
REPOSITORIES: ENA
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Project description:Heterozygous variants in SOX10 cause syndromes affecting pigmentation, digestion, hearing, and neural development, primarily attributable to failed differentiation or loss of non-skeletal neural crest derivatives. We report here an additional novel requirement for Sox10 in bone mineralization. Neither crest- nor mesoderm-derived bones initiate mineralization on time in zebrafish sox10 mutants, despite normal osteoblast differentiation and matrix production. Mutants are deficient in the Trpv6+ ionocytes that take up calcium from the environment, resulting in severe calcium deficiency. As these ionocytes derive from ectoderm, not crest, we hypothesized that the primary defect resides in a separate organ that systemically regulates ionocyte numbers. RNAseq revealed significantly elevated stanniocalcin (Stc1a), an anti-hypercalcemic hormone, in sox10 mutants. Stc1a inhibits calcium uptake in fish by repressing trpv6 expression and Trpv6+ ionocyte proliferation. Epistasis assays confirm excess Stc1a as the proximate cause of the calcium deficit. The pronephros-derived glands that synthesize Stc1a interact with sox10+ cells, but these cells are missing in mutants. We conclude that sox10+ crest-derived cells non-autonomously limit Stc1a production to allow the inaugural wave of calcium uptake necessary to initiate bone mineralization.
2025-01-07 | GSE283071 | GEO
Project description:We have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study. Human melanoma cell line M010817 was transfected with either control shRNA or SOX10 shRNA. RNA was isolated at 48 hours and 96 hours after transfection and subjected to hybridization on Affymetrix microarrays.
2012-07-02 | E-GEOD-37059 | biostudies-arrayexpress
Project description:We have shown that Sox10 plays a crucial role in the initiation and maintenance of giant congenital nevi and melanoma in a mouse model of melanoma.To dissect the molecular mechanisms and analyze the role of SOX10 in the maintenance of human melanoma, we have performed microarray study.
2012-07-03 | GSE37059 | GEO
Project description:ChIP-seq of Sox10 in spinal cord and sciatic nerve was performed to determine shared and unique binding sites for Sox10 in oligodendrocytes and Schwann cells, respectively. Sox10 is required for both Schwann cell and oligodendrocyte development. In addition, differentiation of myelinating glia is dependent upon axonal signaling, so these studies were performed in vivo.
2015-04-01 | GSE64703 | GEO
Project description:YAP1 and WWTR1 are required for murine pregnancy initiation
| PRJNA1112897 | ENA
Project description:Given the heterogeneous expression of SOX10 in naïve melanoma, we sought to characterize SOX10 deficient population. To this end, we generated SOX10 CRISPR/Cas9 knockouts using two different guide RNAs (gRNA, #2 and #4) in the A375 (BRAF mutant) metastatic cell line. Using this approach, we identified multiple clones with loss of SOX10 expression. RNA-seq was performed to characterize the SOX10-regulated transcriptome. We used GSEA analysis to evaluate significant pathway changes in SOX10 knockout cells when compared to parental cells. We observed an enrichment in pathways associated with the tumor microenvironment (epithelial-mesenchymal transition; TGF beta signaling; extracellular structure organization; apical junction; hypoxia; angiogenesis), alterations in metabolic pathways (increase in the glycolysis pathway), a reduction in MYC and E2F targets and upregulation in p53 pathway and TNFA signaling via NFkB in the SOX10 knockout cells compared to parental cells. SOX10 negative clones have been identified in the minimal residual disease in BRAF mutant PDX models following BRAF and MEK inhibition and in patient samples while on treatment and SOX10 loss has been described as a resistant mechanism in BRAF mutant melanoma patients following vemurafenib treatment. Thus, we also analyzed the transcriptome profile of SOX10 low/deficient cells that arose following BRAFi+MEKi treatment in vivo. We performed GSEA analysis on RNA-seq data of CRT34 and CRT35 cells compared to parental A375 cells. CRT34 and CRT35 showed a very similar transcriptome profile to SOX10 KO cells when compared to A375 parental cells
2022-01-24 | GSE180568 | GEO
Project description:Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G-protein coupled receptors (GPCRs) function as transducers of external signals by activating associated G-proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, though their activities in tooth development remains poorly understood. The present results show that the adhesion-GPCR Gpr115 (Adgrf4) is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the in vivo function of Gpr115, knockout (Gpr115-KO) mice were created and found to develop hypo-mineralized enamel, with a larger acidic area due to the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of Gpr115 disrupted pH homeostasis and ion transport processes in enamel formation. In addition, in vitro analyses using the dental epithelial cell line Cervical Loop-Derived Dental Epithelial (CLDE) cell demonstrated that Gpr115 is indispensable for the expression of carbonic anhydrase 6 (Car6), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced Car6 expression under the regulation of Gpr115 in CLDE cells. Thus, we concluded that Gpr115 plays an important role in enamel mineralization via regulation of Car6 expression in ameloblasts. The present findings indicate a novel function of Gpr115 in ectodermal organ development and clarify the molecular mechanism of enamel formation.
2020-08-31 | GSE155641 | GEO
Project description:The transcription factor SRY(sex related protein-Y)-box10 (SOX10) plays a key role in the development of melanocytes and peripheral glial cells from neural crest precursors. Recently, we and other groups found SOX10 to be involved in melanoma initiation, proliferation, invasion, and survival. However, specific mediators which impart the oncogenic role of SOX10 in melanoma remain widely unknown. To identify potential target genes of SOX10, we performed RNA sequencing to analyze genome-wide expression alterations after ectopic expression of SOX10. Among nine genes differentially regulated by SOX10, only peripheral myelin protein 2 (PMP2) was found upregulated in several other melanoma cell lines. PMP2 is one of the most abundant myelin proteins in glial cells and is necessary for the formation and maintenance of the myelin sheath. We detected PMP2 expression in a subset of human melanoma cell lines while it was absent in human melanocytes and fibroblasts. Direct binding of SOX10 to the PMP2 promoter was shown by chromatin immunoprecipitation and electrophoretic shift assay. In three-dimensional spheroid assays, we found that PMP2 overexpression increased melanoma cell invasion. In conclusion, we identified PMP2 as target gene of SOX10 and propose a novel role for PMP2 in melanoma cell invasion.
2017-12-31 | GSE79988 | GEO
Project description:G-protein coupled receptor Gpr115 (Adgrf4) is required for enamel mineralization mediated by ameloblasts
| PRJNA650531 | ENA
Project description:We report sequencing data on fetal mouse submandibular glands (SMGs) where SOX10 was deleted in the epithelia. By obtaining embryonic day 16 (E16) SMGs, we compared control glands with glands where SOX10 was deleted in the epithelial compartment. We found that loss of SOX10 resulted in smaller glands, which had reduced expression of genes related to the initiation of acinar, myoepithelial and intercalated duct cells.
2019-03-06 | GSE123341 | GEO