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SOX9 Haploinsufficiency reveals SOX9-Noggin to BMP-SMAD signaling pathway in chondrogenesis

ABSTRACT: SOX9 Haploinsufficiency reveals SOX9-Noggin to BMP-SMAD signaling pathway in chondrogenesis

PROVIDER: PRJNA1065780 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27588224_1.fastq.gz	Fastqsanger.gz
	SRR27588224_2.fastq.gz	Fastqsanger.gz
	SRR27588225_1.fastq.gz	Fastqsanger.gz
	SRR27588225_2.fastq.gz	Fastqsanger.gz
	SRR27588226_1.fastq.gz	Fastqsanger.gz

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SOX9 Haploinsufficiency reveals SOX9-Noggin to BMP-SMAD signaling pathway in chondrogenesis

Project description:SOX9 is well-known for its role in chondrogenesis and gonadogensis. Campomelic Dysplasia (CD) is an example of SOX9 haploinsufficiency-caused rare congenital disease, in which the patients are reported to have skeletal abnormalities. In this study, we created a hiPSC-modeling CD patient and investigated the effect of SOX9 on the regulation of chondrocyte differentiation in BMP-SMAD signaling in vitro. In the CD patient transcriptome, the BMP-SMAD signaling pathway and ribosome-related and chromosome segregation-related gene sets were altered. Upon further experimentation, noggin was found to be significantly upregulated in HT and HM mutants. The overexpression of SOX9 also showed upregulation in SOX9 and COL2A1. . We hope this finding can give a better picture of the dosage-dependent role of SOX9 in chondrogenesis and reveal the manifestation of skeletal dysplasia in CD patients, thereby helping to develop better drugs for these patients.

2025-03-04 | GSE253431 | GEO

SOX9 haploinsufficiency reveals SOX9-Noggin interaction in BMP-SMAD signaling pathway in chondrogenesis.

Project description:Campomelic Dysplasia (CD) is a rare congenital disease caused by haploinsufficiency (HI) in SOX9. Patients with CD typically present with skeletal abnormalities and 75% of them have sex reversal. In this study, we use CRISPR/Cas9 to generate a human induced pluripotent stem cell (hiPSC) model from a heathy male donor, based on a previously reported SOX9 splice site mutation in a CD patients. This hiPSCs-derived chondrocytes from heterozygotes (HT) and homozygotes (HM) SOX9 mutation carriers showed significant defects in chondrogenesis. Bulk RNA profiling revealed that the BMP-SMAD signaling pathway, ribosome-related, and chromosome segregation-related gene sets were altered in the HT chondrocytes. The profile also showed significant noggin upregulation in CD chondrocytes, with ChIP-qPCR confirming that SOX9 binds to the distal regulatory element of noggin. This suggests SOX9 plays a feedback role in the BMP signaling pathway by modulating noggin expression rather than acting solely as a downstream regulator. This provides further insights into its dosage sensitivity in chondrogenesis. Overexpression of SOX9 showed promising results with improved sulfated glycosaminoglycans (GAGs) aggregation and COL2A1 expression following differentiation. We hope this finding could provide a better understanding of the dosage-dependent role of SOX9 in chondrogenesis and contribute to the development of improved therapeutic targets for CD patients.

| S-EPMC11872873 | biostudies-literature

Profiling of Sox9-related genes in chondrogenesis using Sox9-3'EGFP knock-in and Sox9-EGFP/EGFP null chimeric mouse embryos

Project description:To define the repertoire of Sox9-dependent genes that contribute to the regulation of chondrogenesis, we generated Sox9-3'enhanced green fluorescent protein (EGFP) knock-in mice (Sox9-3'EGFP) and Sox9-EGFP/EGFP null chimeras. EGFP-positive cells of Sox9-3'EGFP knock-in and Sox9-EGFP/EGFP null chimeric embryos harvested from limb buds at embryonic day 12.5 were sorted using a FACSAria flow cytometer (Becton-Dickinson). Total RNA of sorted cells was extracted using the RNeasy Mini Kit (QIAGEN) and amplified according to the instructions provided by Affymetrix. Microarray analysis using the Affymetrix Mouse Genome 430 2.0 Array was performed according to the manufacturer's instructions.

2011-02-16 | E-MTAB-537 | biostudies-arrayexpress

The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis (ChIP-Seq)

Project description:SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We used RNA-seq to charatierize a rat chondrosarcoma (RCS) cells as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes and ChIP-seq to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. ChIP-seq for SOX9, SOX6 and histone modifications were carried out using RCS cells

2015-06-23 | E-GEOD-70143 | biostudies-arrayexpress

SOX9 is dispensable to initiate epigenetic remodeling and activation of marker genes at the onset of chondrogenesis (ChIP-Seq)

Project description:Using whole-transcriptome and whole-epigenome sequencing approaches for wild-type and Sox9-deficient mouse embryo limb buds, we here identify genes specifically expressed and likely involved in precartilaginous condensation. We show that SOX9 directly upregulates these genes and well-known early-cartilage markers, and that its actions in chondrogenic cells have little impact on neighboring cell types. Intriguingly, we find that SOX9 helps remove epigenetic signatures of transcriptional repression and establish active-promoter and active-enhancer marks at precartilage- and cartilage-specific loci, but is not absolutely required to initiate these changes and activate transcription. Altogether, these findings widen our current knowledge of SOX9 targets in early chondrogenesis and call for new studies to identify the pioneer and transactivating factors that act upstream of or along with SOX9 to prompt chromatin remodeling and specific gene activation at the onset of chondrogenesis and other processes.

2018-07-02 | GSE114520 | GEO

SOX9 is dispensable to initiate epigenetic remodeling and activation of marker genes at the onset of chondrogenesis (RNA-Seq)

2018-07-02 | GSE114521 | GEO

The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis (RNA-Seq)

Project description:SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We used RNA-seq to charatierize a rat chondrosarcoma (RCS) cells as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes and ChIP-seq to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. RNAs were isolated from three bioogical replicatse of rat chondrosarcoma (RCS) cells and rib samples for RNA-seq experiments.

2015-06-23 | E-GEOD-70142 | biostudies-arrayexpress

The protein kinase MLTK Is a key regulator for chondrogenesis.

Project description:Sox9 acts together with Sox5 or Sox6 as a master regulator for chondrocyte differentiation; however, how these transcription factors functionally interact and collaborate to regulate chondrogenesis remains unclear. Here we show that the protein kinase MLTK plays an essential role in the onset of chondrogenesis through triggering the induction of Sox6 by Sox9. Knockdown of MLTK in Xenopus embryos results in drastic loss of craniofacial cartilages without defects in neural crest formation. We also find that Sox6 is specifically induced during craniofacial chondrogenesis and this induction is inhibited by MLTK knockdown. Remarkably, Sox6-knockdown embryos display essentially the same phenotype as the MLTK-knockdown embryos; the drastic loss of cartilages and the marked down-regulation of genes involved in chondrogenesis. Microarray analysis reveals a remarkable similarity between Sox6-depleted and MLTK-depleted embryos in their gene expression pattern. Moreover, we find that ectopic expression of MLTK can induce Sox6 expression in a Sox9-dependent manner. These results identify a novel, key regulator for chondrogenesis. We used microarrays to describe the genome-wide gene expression profiles of xMLTK-depleted and xSox6-depleted embryos.

2012-09-04 | GSE33767 | GEO

The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis (ChIP-Seq)

2015-06-23 | GSE70143 | GEO

The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis (RNA-Seq)

2015-06-23 | GSE70142 | GEO