Elisabeth, B Wong
| Elisabeth, B Wong |
Elisabeth, B Wong1, Xiaobin Huang2
Chider Chen2
1Basic and Translational Science, University of Pennsylvania, School of Dental Medicine; 2Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, School of Dental Medicine
Introduction
Prenatal growth is faster than during any other period of life, which is mainly attributed to the superior stemness of somatic stem cells. However, molecular signatures regulating distinct stem cell state and functionality are still largely unknown. In this study, we compared mesenchymal stem cells from newborn mice (nMSCs) with MSCs from adult (12 weeks) mice (aMSCs) to explore the regulatory mechanisms during stem cell reprograming.
Methods
MSCs were isolated from newborn and adult mice for RNA-sequencing analysis. The gene ontology (GO) enrichment analysis, the Kyoto encyclopedia of genes and genomes (KEGG) analysis, and the gene set enrichment analysis (GSEA) were used to identify gene sets and signaling pathways that are significantly enriched between groups. To study skeletal morphology, bone tissues were harvested and analyzed using a high-resolution Scanco MicroCT (μCT50) scanner, followed by reconstructing images and measuring bone mineral density (BMD).
Results
RNA-seq analysis identified the gene-sets enriched in nMSCs are associated with lineage differentiation, cell cycle, and mitochondrial metabolism. In addition, nMSCs highly rely on mitochondrial oxidative phosphorylation (OxPhos) to generate more energy to fulfill biosynthetic requirements during rapid proliferative developmental stage, whereas aMSCs exhibit a quiescence status by using glycolysis to maintain microenvironmental homeostasis. Mechanistically, Pgc-1, as the master regulator of mitochondrial biogenesis, is required for the enhanced OxPhos activity and proliferation and multipotent differentiation in nMSCs. Consistent with the RNA-seq analysis, deletion of Pgc-1 significantly reduced BMD and disrupted skeletal structure when compared to control littermates.
Conclusion
In summary, this study explores a novel metabolic reconfiguration during stem cell transition from developmental to adult stages.