Project description:Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized tissue. Bulk RNA sequencing revealed that up- and down-regulated genes in ciOG relative to aHDF resembled those in hOB during maturation.
Project description:Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized tissue. When generated on a nanofiber substrate ciOG accelerated osteogenic gene expressions and mineralization compared to PCL film followed by bone matrix formation in a calvarial defect, indicating that the engineered biomaterial promotes the osteogenic capacity of ciOG in vivo.
Project description:Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized tissue. Single-cell RNA sequencing analysis of ciOG identified unique clusters of cells, among which the cluster of active cells related to osteogenic cells was ~49% of the cells, or ~80% of active cells; another cluster of active cells (~12% of the cells) was related to fibroblasts. The reprogramming trajectory over time revealed the transition from fibroblasts to mainly osteogenic cells or to an inactive state.