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Mus musculus

ABSTRACT: Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (RNA-seq)

PROVIDER: PRJNA317058 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3319790.fastq.gz	Fastqsanger.gz
	SRR3319800.fastq.gz	Fastqsanger.gz
	SRR3319791.fastq.gz	Fastqsanger.gz
	SRR3319801.fastq.gz	Fastqsanger.gz
	SRR3319792.fastq.gz	Fastqsanger.gz

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Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells

Project description:Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells

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Extracellular vesicles from osteogenic differentiated human BMSCs

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Mus musculus

Project description:Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (ChIP-seq)

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Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (RNA-seq)

Project description:Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSC). As assessed by ChIP-seq and RNA-seq analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, RXR, and VDR binding sites, whereas adipocyte differentiation favored PPARγ, RXR, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice-versa) after commitment, as assessed by staining, gene expression, and ChIP-qPCR analysis. The osteogenic default pathway may be subverted during pathological conditions leading to skeletal fragility and increased marrow adipocity during aging, estrogen deficiency and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies.

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Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (ChIP-seq)

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Project description:Adipose tissue harbours a significant number of multipotent adult stem cells of mesenchymal origin known as adipose-derived stem cells (ADSCs). Broad differentiation potential and convenient accessibility of ADSCs make them an attractive source of adult mesenchymal stem cell for regenerative medicine and cell developmental plasticity research. Genome-wide microarray expression profiling was performed to identify genes deregulated during osteogenic differentiation of ADSCs to evaluate developmental plasticity of these cells. Dynamics of epigenetic modifications were analyzed in parallel and associated with the gene expression profile. Gene expression profile was analyzed in adipose-derived stem cells (ADSCs) differentiated into osteogenic lineage from 3 donors and compared to undifferentiated cells from the same donors.

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MiR-30e in Aortic Smooth Muscle Cells and Bone Marrow Mesenchymal Stem Cells [Experiment 3]

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MiR-30e in Aortic Smooth Muscle Cells and Bone Marrow Mesenchymal Stem Cells [Experiment 2]

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MiR-30e in Aortic Smooth Muscle Cells and Bone Marrow Mesenchymal Stem Cells [Experiment 3]

Project description:MiR-30e represses the osteogenic program in mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs) by targeting IGF2, and drives their differentiation into adipogenic or smooth muscle lineage, respectively. In Experiment 1, SMCs were cultured from mouse aortas and transduced with miR-30e or control lentivirus. In Experiment 2, MSCs were extracted from mouse bone marrow and transduced with miR-30e or control lentivirus. In Experiment 3, the MSCs were transfected with a scrambled oligo or anti-miR-30e oligo. In all 3 experiments, N=3 per group. RNA was extracted from each experiment and run on Affymetrix arrays.

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