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Series GSE79814 Query DataSets for GSE79814
Status Public on Jul 11, 2016
Title Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells (RNA-seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
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 mRNA isolation and sequencing.
Contributor(s) Meyer MB, Benkusky NA, Pike JW
Citation(s) 27402842
Submission date Apr 01, 2016
Last update date May 15, 2019
Contact name Mark B Meyer
Phone 608-890-0857
Organization name University of Wisconsin-Madison
Department Nutritional Sciences
Lab Meyer Lab
Street address 1415 Linden Dr.
City Madison
State/province WI
ZIP/Postal code 53706
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (24)
GSM2104258 MSCD0_Veh_rep1
GSM2104259 MSCD0_Veh_rep2
GSM2104260 MSCD0_Veh_rep3
This SubSeries is part of SuperSeries:
GSE79815 Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells
BioProject PRJNA317058
SRA SRP072737

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE79814_RAW.tar 3.6 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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