GSE105145
Bone marrow-derived and dental pulp-derived human mesenchymal stem cell RNA-Seq
Lineage commitment and tumorigenesis specify adult stem cells from different tissues or organs. To gain insight into the mechanism of this programming, phenotypic, functional and transcriptome analyses were performed in mesenchymal stem cells derived from human dental pulp (DPSCs) and bone marrow (BMSCs). DPSCs and BMSCs had similar morphologies and flow cytometric profiles, and were capable of tri-lineage differentiation into osteoblast, adipocyte and chondocyte. However, compared with BMSCs, DPSCs increased in osteogenic potential, decreased in adipogenic potential, and formed dentin-pulp-like complexes in vivo. Genome-wide RNA-seq and differential expression analysis revealed that signalings such as, phosphatase and tensin homolog (PTEN)/PI3K/AKT pathway, and cancer-related pathway were different in both cells. Differential PTEN expression, higher in DPSCs than BMSCs, was responsible for the lineage commitment and tumorigenesis differences in both cells. Besides, BMSCs decreased in PTEN DNA methylation compared to DPSCs, which was mediated by increased DNA (cytosine-5) methyltransferase 3B (DNMT3B) expression. Furthermore, histone methyltransferase G9a mediated repressive epigenetic mark H3K9Me2 was selectively enriched in BMSCs. Moreover, DPSCs were more resistant to oncogenic transformation than BMSCs. To link lineage commitment with tumorigenesis, we demonstrated that DPSCs were more resistant to oncogenic transformation than BMSCs and PTEN deficiency increased the sensitivity of DPSCs for tumorigenic transformation. The results help understanding the roles of the epigenetic factors in lineage commitment and tumorigenesis and also for therapeutic uses of adult stem cells. Overall design: RNA-Seq of bone marrow-derived and dental pulp-derived mesenchymal stem cells with 3 biological replicates