Human amnion and chondrosarcoma

Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly specify somatic cell fates in cells such as pancreatic β cells, contractile cardiomyocytes and neurons. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes (5F pool), BCL6, T (also called BRACHYURY), c-MYC, MITF and BAF60C (also called SMARCD3) that rapidly and efficiently convert postnatal human amnion into chondrosarcoma. The cells generated expressed multiple cartilage-specific genes such as collagen type II α1, link protein-1 and aggrecan, and exhibited characteristics of cartilage both in vivo and in vitro. Expression of the endogenous genes for T and MITF was initiated, implying that the cell conversion is due to not only the forced expression of the transgenes, but also the cellular reprogramming by the transgenes. The same set of genes converted human placental artery-derived endothelial (hPAE) cells and menstrual blood-derived cells into chondrosarcoma cells, implying that this conversion is independent of cell types. Direct conversion system from non-cartilage tissue to cartilaginous tissue contributes substantially to a major advance toward cartilage development, oncogenesis of chondrocytes, and cell-based therapy. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes that rapidly efficiently convert postnatal human amnion into chondrosarcoma.