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| Status |
Public on Jul 11, 2016 |
| Title |
Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Marrow derived MSC cells were differentiated to day 7 or day 15 with osteogenic or adipogenic media. These cells were then treated with vehicle or 100nM 1,25(OH)2D3 for 24 hours prior to ChIP assay, library creation and sequencing.
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| Web link |
https://biochem.wisc.edu/labs/pike/data-sets-pike-lab
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| Contributor(s) |
Meyer MB, Benkusky NA, Pike JW |
| Citation(s) |
27402842 |
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| Submission date |
Apr 01, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Mark B Meyer |
| E-mail(s) |
markmeyer@wisc.edu
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| Phone |
608-890-0857
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| Organization name |
University of Wisconsin-Madison
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| Department |
Nutritional Sciences
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| Lab |
Meyer Lab
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| Street address |
1415 Linden Dr.
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53706 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (144)
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| This SubSeries is part of SuperSeries: |
| GSE79815 |
Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells |
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| Relations |
| BioProject |
PRJNA317059 |
| SRA |
SRP072735 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79813_RAW.tar |
9.6 Gb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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