Transcriptional changes after YAP/TAZ siRNA-mediated knockdown, and BMP-2 stimulation and SMAD1 ChIP-Seq in BMP2-treated human fetal osteoblasts
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ABSTRACT:
PROVIDER: PRJNA564311 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10080417_1.fastq.gz | Fastqsanger.gz | |||
| SRR10080417_2.fastq.gz | Fastqsanger.gz | |||
| SRR10080418_1.fastq.gz | Fastqsanger.gz | |||
| SRR10080418_2.fastq.gz | Fastqsanger.gz | |||
| SRR10080419_1.fastq.gz | Fastqsanger.gz |
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Project description:Osteogenesis is influenced by a variety of factors including growth factors - especially those of the TGF-beta superfamily - and Hippo signaling. Consequently, we hypothesize that the YAP/TAZ pathway is intertwining with TGF-beta and BMP signaling resulting in osteogenic differentiation. Therefore, we performed a comprehensive RNA-Seq study including both YAP/TAZ depletion by siRNA and BMP stimulation conditions in human fetal osteoblasts cell line hFOB 1.10. In order to identify the direct SMAD1 target genes corresponding to our RNA-Seq data, we performed an SMAD1 chromatin immunoprecipitation followed by sequencing.
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Project description:The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.
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