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RNF4-RGMb axis is required for osteogenic differentiation and cancer cell survival

ABSTRACT: RNF4-RGMb axis is required for osteogenic differentiation and cancer cell survival

PROVIDER: PRJNA845209 | ENA |

REPOSITORIES: ENA

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RNF4-RGMb axis is required for osteogenic differentiation and cancer cell survival

Project description:Molecular understanding of osteogenic differentiation (OD) of human bone-marrow derived mesenchymal stem cells (hBMSCs) is important for regenerative medicine and has direct implications to cancer. Here we report that the RNF4 ubiquitin ligase is essential for OD of hBMSCs, and that RNF4 deficient hBMSCs fail to differentiate and remain as stalled progenitors. Remarkably, addition of media from differentiating hBMSCs to RNF4-deficient MSCs alleviated the block in OD. Transcriptional analysis of RNF4-dependent gene signature identified two secreted factors; BMP6 and the guidance molecule BMP6 co-receptor RGMb (Dragon). Knockdown of either RGMb or BMP6 in hBMSCs inhibit differentiation, and only the combined addition of purified RGMb and BMP6 proteins to RNF4-deficient MSCs fully restored osteogenic differentiation. Moreover, RNF4-RGMb axis is highly relevant cancer cell survival and tumorigenicity, including osteosarcoma and Therapy-resistant melanoma cells. In accordance, in human melanoma biopsies high level of RGMb correlates with high level of RNF4, and is associated with resistance to molecular therapy and poor prognosis of patients. Thus, RNF4~BMP6~RGMb is a molecular axis that is key for OD and tumorigenesis.

2022-09-28 | GSE205432 | GEO

Sexual dimorphism in osteogenic differentiation

Project description:Sexual dimorphism in osteogenic differentiation

| PRJNA768873 | ENA

Visceral Endoderm differentiation mediated by Hnf1B and is required for epiblast survival

Project description:Visceral Endoderm differentiation mediated by Hnf1B and is required for epiblast survival

| PRJEB49826 | ENA

Sexual dimorphism in osteogenic differentiation

Project description:RNA-sequencing of adult human stem cells determining sexual dimorphisms in osteogenic differentiation.

2022-03-10 | GSE185394 | GEO

Different osteogenic differentiation behavior of canine mesenchymal stem cells derived from bone marrow and dental pulp: the proteomics profile

Project description:Although various sources of cMSCs show similar characteristics, they are different in osteogenic potential due to their original cellular sources. Thus, this study was designed to globally explore and analyze the in vitro differentiation potential and behavior of canine bone-marrow derived mesenchymal stem cells (cBM-MSCs) and canine dental pulp stem cells (cDPSCs) toward osteogenic lineage. Global study of an in vitro osteogenic differentiation potential of the isolated cells was performed using proteomic-based analysis through mass spectrometry with dimethyl labelling method at day 7 and 14 post-induction, comparing with undifferentiated cells. The obtained results could be used as a comprehensive data and principal knowledge of the osteogenic differentiation potential of cBM-MSCs and cDPSCs in vitro and the trend of MSC-based tissue engineering for osteogenic regenerative therapy, concentrating on cMSCs application.

2021-09-08 | PXD015512 | Pride

Transcription profiling of human mesenchymal stem cell osteogenic differentiation

Project description:full human genome expression microarrays were used to analysis of gene expression profiles upon the induction of MSC osteogenic differentiation.

2009-05-31 | E-MEXP-2131 | biostudies-arrayexpress

PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells (4C-seq)

Project description:The PLZF transcription factor is essential for osteogenic differentiation of hMSCs, however, its regulation and molecular function during this process is not fully understood. Here we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naïve hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation.

2019-01-17 | GSE125165 | GEO

PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells (RNA-seq)

2019-01-17 | GSE125167 | GEO

PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells (ChIP-seq)

2019-01-17 | GSE125166 | GEO

CHD7 regulates osteogenic differentiation of human dental follicle cells via PTH1R signaling

Project description:Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here we show CHD7 expression increases with osteogenic differentiation. knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and decreased expression of osteogenesis-related genes. Conversely, CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the down-regulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.

2020-07-22 | GSE154822 | GEO

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