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Global comparative transcriptome analysis of cartilage formation in vivo

ABSTRACT: We set out to characterize the gene expression changes which take place during chondrogenesis in the developing mouse limb. RNA derived from pre-condensed mesenchyme, mesenchymal condensations, and cartilage anlagen representing the earliest stages of tibial and fibular development was analysed by whole genome microarray analysis, and revealed 931 genes differentially expressed in these tissues. Among them were 892 genes not previously identified during the initation of chondrogenesis, including members of the Bmp, Wnt, Gdf, Sox, and Fox gene families. These microarray data were validated by qPCR, in situ hybridisation, and analysis of numerous genes already implicated in chondrogenesis in the scientific literature.

ORGANISM(S): Mus musculus

PROVIDER: GSE35669 | GEO | 2012/02/10

SECONDARY ACCESSION(S): PRJNA152441

REPOSITORIES: GEO

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Global comparative transcriptome analysis of cartilage formation in vivo

Project description:We set out to characterize the gene expression changes which take place during chondrogenesis in the developing mouse limb. RNA derived from pre-condensed mesenchyme, mesenchymal condensations, and cartilage anlagen representing the earliest stages of tibial and fibular development was analysed by whole genome microarray analysis, and revealed 931 genes differentially expressed in these tissues. Among them were 892 genes not previously identified during the initation of chondrogenesis, including members of the Bmp, Wnt, Gdf, Sox, and Fox gene families. These microarray data were validated by qPCR, in situ hybridisation, and analysis of numerous genes already implicated in chondrogenesis in the scientific literature. 231 sections from a total of four 11.5dpc mouse hind limbs, three 12.5dpc mouse hind limbs, and four 13.5dpc mouse hind limbs (all from separate mice) were microdissected, and tissues from each time point were pooled. Thus, this experiment consisted of one replicate only.

2012-02-10 | E-GEOD-35669 | biostudies-arrayexpress

Skeletal stem/progenitor cells in periosteum and skeletal muscle share a common molecular response to bone injury

Project description:Periosteum is a major source of skeletal stem/progenitor cells (SSPCs) during bone repair. However, the cellular composition of the periosteum is poorly characterized. Here, we provide single-cell RNAseq data of periosteal cells isolated by explant culture at steady state and at day 3 post-tibial fracture. We found that periosteal cell populations are heterogeneous containing several sub-populations of SSPCs. Upon fracture, SSPCs are activated by leaving their mesenchymal state, and engaging into fibrogenesis prior to chondrogenesis.

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Gene expression profile at single cell level of HeLa cells treated with the CDC7-specific inhibitor TAK-931 [scRNA-seq]

Project description:We performed scRNA-seq analyses to determine the transcriptional landscape of the TAK-931-induced aneuploid cells at the single-cell levels. HeLa cells were treated with DMSO or TAK-931 (300 nM) for 72 h. In the t-SNE plots, the DMSO- and TAK-931-treated cells were classified in two distinct clusters. Indicating that the major population of the TAK-931-treated aneuploid HeLa cells was transformed to a cell contexture that was transcriptionally distinct from that of DMSO-treated control cells. The hallmark of an inflammatory response was remarkably enriched in the TAK-931 treatment cluster. In addition, the positive cells of inflammatory cytokine/chemokine-related genes, such as CXCL8, IL1B, TNHSF14 and TNFRSF1B, were significantly accumulated in the TAK-931-treatment cluster.

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Project description:Escherichia coli strain:892 | isolate:892 Genome sequencing

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Program specificity for Ptf1a in Pancreas versus Neural Tube Development correlates with distinct collaborating cofactors and chromatin accessibility

Project description:Ptf1a is a lineage-specific basic-helix-loop-helix transcription factor critical in the development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. A majority of regions bound by Ptf1a are tissue-specific, lie near genes needed for proper formation and maturation of each tissue, and reflect regions of open chromatin. Information for the specificity of Ptf1a binding and function is encoded in the DNA surrounding the Ptf1a-bound sites, since Ptf1a-bound regions are sufficient to direct tissue-restricted reporter expression when tested in transgenic mice. Fox and Sox factors were identified as lineage specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Although Ptf1a and Foxa2 co-localize to sites in embryonic pancreas and can act synergistically in cell transfection assays, biochemical experiments detected no physical interaction between the two factors. These findings indicate that lineage-specific chromatin landscapes likely constrain the functions of Ptf1a, and identify Fox and Sox gene families as part of this process.

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Project description:Osteoarthritis (OA) is the most prevalent chronic joint disease that affects a majority of the elderly. Chondrogenic progenitor cells (CPCs) reside in late stage OA cartilage tissue, producing a fibrocartilagenous extra-cellular matrix and can be manipulated in-vitro, to deposit proteins of healthy articular cartilage. CPCs are under control of SOX9 and RUNX2 and in order to enhance their chondrogenic potential, we found that RUNX2 plays a pivotal role in chondrogenesis. In another approach, CPCs carrying a knockout of RAB5C, a protein involved in endosomal trafficking, demonstrated elevated expression of various chondrogenic markers including the SOX trio and displayed an increased COL2 deposition, whereas no changes of COL1 deposition was observed. We report RAB5C as an attractive target for future therapeutic approaches to increase the COL2 content in the diseased joint.

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GDF-15 is a biomarker of aggressiveness and is down-regulated by the mTOR inhibitor sirolimus through ATF4 and ATF5 suppression in epithelioid hemangioendothelioma.

Project description:Growth and differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, exhibits elevated expression in various tumor types, often linked to disease aggressiveness. In this study, which used patient-derived xenografts and paired cell lines of epithelioid hemangioendothelioma (EHE), it was found that EHE cells produce and release GDF-15. Furthermore, the mTOR inhibitor sirolimus was observed to inhibit GDF-15 expression and release by down-regulating ATF4 and ATF5 transcription factors. To assess the clinical relevance of GDF-15 in EHE, which can manifest as both relatively indolent and exceptionally aggressive forms, circulating GDF-15 levels were assessed in two independent cohorts of EHE patients, one retrospective and one prospective. The results provided evidence of an association between circulating GDF-15 levels and the aggressiveness of EHE. In summary, these findings suggest that GDF-15 can serve as a biomarker for EHE aggressiveness and may have implications for monitoring the effectiveness of sirolimus in EHE patients.

2024-04-24 | GSE246235 | GEO

GDF-15 is a biomarker of aggressiveness and is down-regulated by the mTOR inhibitor sirolimus through ATF4 and ATF5 suppression in epithelioid hemangioendothelioma.

2024-04-24 | GSE246152 | GEO

Project description:GDF-induced

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Program specificity for Ptf1a in PancreasM-BM- versusM-BM- Neural Tube DevelopmentM-BM- correlates with distinctM-BM- collaborating cofactors and chromatin accessibility

Project description:Ptf1a is a lineage-specific basic-helix-loop-helix transcription factor critical in the development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regions in vivo during development of both tissues. A majority of regions bound by Ptf1a are tissue-specific, lie near genes needed for proper formation and maturation of each tissue, and reflect regions of open chromatin.M-BM- M-BM- Information for the specificity of Ptf1a binding and function is encoded in the DNA surrounding the Ptf1a-bound sites, since Ptf1a-bound regions are sufficient to direct tissue-restricted reporter expression when tested in transgenic mice. Fox and Sox factors were identified as lineage specific modifiers ofM-BM- Ptf1a binding, sinceM-BM- binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Although Ptf1a and Foxa2 co-localize to sites in embryonic pancreas and can act synergistically in cell transfection assays, biochemical experiments detected no physical interaction between the two factors. These findingsM-BM- indicateM-BM- that lineage-specific chromatin landscapes likely constrain the functions of Ptf1a, and identify Fox and Sox gene families as part of this process. RNA-Seq: Examination of gene expression in Ptf1a expressing cells (NT E.12.5, Pancreas E15.5) ChIP-Seq: Examination of chromatin occupancy in 2 tissue types (E12.5 NT and 17.5 Pancreas). Faire-Seq: Examination of open chromatin in 2 tissue types (E12.5 NT and 17.5 Pancreas).

2013-08-15 | E-GEOD-47459 | biostudies-arrayexpress

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