STAT5A knockout endows fibroblasts with features of young mesenchymal stem cells

Fibroblasts and mesenchymal stem cells are very similar in cell morphology and expression of specific antigens on the cell surface. There are studies indicating that fibroblasts can be derived from mesenchymal stem cells, while there has also been a report suggesting that fibroblasts can be dedifferentiated into mesenchymal stem cells. However, the key factor/ gene that regulates the mutual transition between fibroblasts and mesenchymal stem cells has not been fully elucidated. Here we report that knocking out STAT5A in fibroblasts can make fibroblasts gain multipotent differentiation capability similar to that of mesenchymal stem cells and that STAT5A knockout fibroblasts are closer to mesenchymal stem cells in terms of molecular characteristics. STAT5A knockout fibroblasts also acquired immunomodulatory capabilities similar to the capabilities of mesenchymal stem cells and showed multiple characteristics of cellular rejuvenation. After transplantation of human STAT5A knockout fibroblasts into old immunodeficient mice, they can differentiate into osteoblasts in vivo and significantly improve the number and density of lumbar trabecular bone, besides, they do not form tumors. Transplantation of human STAT5A knockout fibroblasts into old NOD/SCID mice significantly reduced senescent cells in multiple tissues. These data indicate that STAT5A is a pivotal factor regulating cellular identity between mesenchymal stem cells and fibroblasts, and STAT5A knockout simultaneously confers multipotent differentiation capacity and youthful characteristics on fibroblasts. Overall design: To elucidate the key factors/genes that regulate the intertransformation between fibroblasts and mesenchymal stem cells