Abstract
Unexpectedly, we found that c-Myc-expressing porcine embryonic fibroblasts (PEFs) subcutaneously implanted into nude mice formed cartilage-like tissues in vivo, while previous studies revealed the direct conversion of mouse and human somatic cells into chondrocytes by the combined use of several defined factors, including c-Myc, which prompted us to explore whether PEFs can be reprogrammed to become pig induced chondrocyte-like cells (piCLCs) via ectopic expression of c-Myc alone. In this study, c-Myc-expressing PEFs, designated piCLCs, which exhibited a significantly enhanced proliferation ability in vitro, displayed a chondrogenic phenotypes in vitro, as shown by the cell morphology, toluidine blue staining, alcian blue staining and chondrocyte marker gene expression. Additionally, piCLCs with a polygonal chondrocyte-like morphology were readily and efficiently converted from PEFs by enforced c-Myc expression within 10 days, while piCLCs maintained the chondrocytic phenotype and normal karyotype during long-term subculture. piCLC-derived single clones with a chondrogenic phenotype in vitro exhibited homogeneity in cell morphology and staining intensity compared with mixed piCLCs. Although the mixtures of cartilaginous tissues and tumorous tissues accounted for ~12% (6/51) of all xenografts (51), piCLCs generated stable, homogenous, hyaline cartilage-like tissues without tumour formation at 45 out of the 51 injected sites when subcutaneously injected into nude mice. The hyaline cartilage-like tissues remained for at least 16 weeks. Taken together, these findings demonstrate for the first time the direct induction of chondrocyte-like cells from PEFs with only c-Myc.
Highlights
Introduction cMyc belongs to the Myc family of transcription factors, which includes N-Myc and L-Myc. c-Myc is believed to regulate the expression of 15% of all genes
Our previous study is first to reveal that the enforced expression of c-Myc in porcine embryonic fibroblasts (PEFs) triggered epithelial-like morphological conversion and mesenchymal-epithelial transition (MET) via F-actin reorganization and RhoA/Rock pathway inactivation[9]
We examined whether pig induced chondrocyte-like cells (piCLCs) could be directly induced from PEFs pig fibroblasts by the re-expression of c-Myc alone
Summary
Introduction cMyc belongs to the Myc family of transcription factors, which includes N-Myc and L-Myc. c-Myc is believed to regulate the expression of 15% of all genes. Increasing evidence demonstrates that the proto-oncogene c-Myc is involved in chondrocyte proliferation, differentiation and maturation, as well as bone formation (see Discussion for details)[15,16,17,18,19,20,21]. These above-mentioned findings prompted us to suspect that PEFs can be directly converted into pig induced chondrocyte-like cells (piCLCs) by only c-Myc, which has never been reported. We examined whether piCLCs could be directly induced from PEFs pig fibroblasts by the re-expression of c-Myc alone
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