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Updated: Jul 3, 2026
Isolation, Characterization and MicroRNA-based Genetic Modification of Human Dental Follicle Stem Cells
Published on: November 16, 2018
Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by
Loyal A Goff1, Shayne Boucher, Christopher L Ricupero
1W. M. Keck Center for Collaborative Neuroscience and Rutgers Stem Cell Research Center, Rutgers University, Piscataway, NJ, USA.
Objective:
Human multipotent mesenchymal stromal cells (MSC) have the potential to differentiate into multiple cell types, although little is known about factors that control their fate. Differentiation-specific microRNAs may play a key role in stem cell self-renewal and differentiation. We propose that specific intracellular signaling pathways modulate gene expression during differentiation by regulating microRNA expression.
Materials And Methods:
Illumina mRNA and NCode microRNA expression analyses were performed on MSC and their differentiated progeny. A combination of bioinformatic prediction and pathway inhibition was used to identify microRNAs associated with platelet-derived growth factor (PDGF) signaling.
Results:
The pattern of microRNA expression in MSC is distinct from that in pluripotent stem cells, such as human embryonic stem cells. Specific populations of microRNAs are regulated in MSC during differentiation targeted toward specific cell types. Complementary mRNA expression analysis increases the pool of markers characteristic of MSC or differentiated progeny. To identify microRNA expression patterns affected by signaling pathways, we examined the PDGF pathway found to be regulated during osteogenesis by microarray studies. A set of microRNAs bioinformatically predicted to respond to PDGF signaling was experimentally confirmed by direct PDGF inhibition.
Conclusion:
Our results demonstrate that a subset of microRNAs regulated during osteogenic differentiation of MSCs is responsive to perturbation of the PDGF pathway. This approach not only identifies characteristic classes of differentiation-specific mRNAs and microRNAs, but begins to link regulated molecules with specific cellular pathways.
Insights
MicroRNAs regulate cell differentiation in human mesenchymal stromal cells (MSC). Platelet-derived growth factor (PDGF) signaling influences specific microRNAs during osteogenic differentiation, linking molecular pathways to cell fate.
Area of Science:
- Stem cell biology
- Molecular and cellular biology
- Genomics and transcriptomics
Background:
- Human multipotent mesenchymal stromal cells (MSC) can differentiate into various cell types, but the regulatory factors are not fully understood.
- MicroRNAs (miRNAs) are implicated in stem cell self-renewal and differentiation, potentially mediating cell fate decisions.
- Intracellular signaling pathways are hypothesized to control gene expression during differentiation by modulating miRNA expression.
Purpose of the Study:
- To investigate the role of specific microRNAs in MSC differentiation.
- To identify intracellular signaling pathways that regulate miRNA expression during stem cell differentiation.
- To link specific miRNAs and their regulatory pathways to cell fate determination in MSCs.
Main Methods:
- Performed Illumina mRNA and NCode microRNA expression analyses on MSCs and their differentiated cells.
- Utilized bioinformatic prediction and pathway inhibition to identify miRNAs associated with platelet-derived growth factor (PDGF) signaling.
- Examined miRNA expression patterns in response to PDGF pathway modulation during osteogenesis.
Main Results:
- MSC microRNA expression patterns differ from those of pluripotent stem cells.
- Specific miRNA populations are regulated during MSC differentiation into distinct cell types.
- A subset of miRNAs involved in osteogenic differentiation was confirmed to be responsive to PDGF pathway inhibition.
Conclusions:
- A distinct set of microRNAs is regulated during MSC osteogenic differentiation and responds to PDGF pathway perturbations.
- This study identifies differentiation-specific mRNAs and miRNAs, connecting them to specific cellular signaling pathways.
- The findings provide insights into the molecular mechanisms governing stem cell fate and differentiation.
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