Interaction with Myeloma Suppresses Ciliogenesis and osteogenesis of Bone Marrow Stromal Cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1100471 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28682301_1.fastq.gz | Fastqsanger.gz | |||
| SRR28682301_2.fastq.gz | Fastqsanger.gz | |||
| SRR28682302_1.fastq.gz | Fastqsanger.gz | |||
| SRR28682302_2.fastq.gz | Fastqsanger.gz | |||
| SRR28682303_1.fastq.gz | Fastqsanger.gz |
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Project description:Impaired bone marrow stromal cells (BMSCs) within the bone niche of multiple myeloma (MM) patients are implicated in the development of myeloma bone disease (MBD) and disease progression. However, the specific mechanisms are not yet fully understood.
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Project description:Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of mesenchymal stem cells (MSCs). Stromal communication with cancer cells can influence treatment response. Understanding the cellular interactions within the tumor-bone milieu is critical to the development of novel agents that can reverse bone diseases. Here we identified that bioactive lncRNA RUNX2-AS1 in myeloma cells could be incorporated into exosomes and transmitted to MSCs, thus repressing the osteogenesis of MSCs. RUNX2-AS1, which arises from the antisense strand of RUNX2, was enriched in MSCs derived from MM patients (MM-MSCs). RUNX2-AS1 was capable of forming an RNA duplex with RUNX2 pre-mRNA at overlapping regions and this duplex transcriptionally repressed RUNX2 expression by reducing the splicing efficiency, resulting in decreased osteogenic potential of MSCs. In vivo mouse models, intraperitoneally administered GW4869, an inhibitor of exosome secretion, was found to be effective in prevention of bone loss, sustained by both bone-forming and anticatabolic activities. Therefore, exosomic lncRNA RUNX2-AS1 may serve as a potential therapeutic target for bone lesions in MM. In summary, our results indicated a unique role of exosomic lncRUNX2-AS1 in transferring from MM cells to MSCs in osteogenic differentiation, through a novel exosomic lncRUNX2-AS1/RUNX2 signaling pathway.
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Project description:To investigate the role of coculture treatment of multiple myeloma cells to bortezomib drug resistance, multiple myeloma cells were cocultured with bone marrow mesechymal stem cells
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Project description:Mesenchymal stem/stromal cells (MSCs) derived from the BM of healthy donors (dMSCs) and myeloma patients (pMSCs) were co-cultured with the model myeloma cell line - MM.1S -, and the gene expression profile of MSCs induced by this interaction was analyzed using high density oligonucleotide microarrays. Deregulated genes in co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and inhibition of osteoblasts. Additional genes induced by co-culture were exclusively deregulated in pMSCs and were predominantly associated to RNA processing, the ubiquitine-proteasome pathway, regulation of cell cycle and Wnt signaling.
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Project description:Mesenchymal stromal cells (MSCs) derived from the BM of healthy donors (dMSCs) and myeloma patients (pMSCs) were co-cultured with the model myeloma cell line - MM.1S -, and the gene expression profile of MSCs induced by this interaction was analyzed using high density oligonucleotide microarrays. Deregulated genes in co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and inhibition of osteoblasts. Additional genes induced by co-culture were exclusively deregulated in pMSCs and were predominantly associated to RNA processing, the ubiquitine-proteasome pathway, regulation of cell cycle and Wnt signaling. Primary MSCs from bone marrow (BM) samples of healthy donors (n=8) and multiple myeloma (MM) patients (n=13) were generated as described by Garayoa et al. 2009 (PMID:19357701). Ficoll-Paque density gradient separation medium was used to isolate mononuclear cells from BM aspirates. MSCs were selected by adherence to plastic and subsequently expanded until passage 2 when they were used for co-culture. For the MSC-MM.1S co-cultures we used a 6-well format transwell system with 1 M-BM-5m pore size membrane. Briefly, 2 X 10^4 MSCs were first cultured attached to the lower side of the membrane, and when reached M-bM-^IM-^H 85% confluence 1 X 10^6 MM.1S cells were seeded on the upper side. After 24 h co-culture in RPMI 1640 medium supplemented with 10% FBS and antibiotics, MSCs were recovered by trypsinization, washed once in PBS and stored at -80M-BM-0C in RLT buffer (Qiagen) until RNA extraction. Absence of MM.1S cells in the recovered MSC population was assessed in selected samples by flow cytometry analysis.
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Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
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Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
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