Direct Conversion of Human Preadipocytes into Hematopoietic, Neuronal, and Pancreatic [alpha] Cells by Oct4 and Klf4 Overexpression

Cellular plasticity obtained by natural adaptation or by forced expression of developmental stage and lineage-specific transcription factors converts differentiated cells into three different levels of potency: pluripotent, multipotent (dedifferentiation), and oligo- or unipotent (transdifferentiation). These processes hold promise for regenerative medicine to replace damaged cells and organs through the identification of transcription factors that determine the fate of cellular plasticity. In this study, we report that ectopic expression of Oct4 and Klf4 induces transdifferentiation of human preadipocytes into three different lineages: hematopoietic, neuronal, and pancreatic endocrine cells. Furthermore, ectopic expression of Oct4 is sufficient to induce transdifferentiation of preadipocytes into glucagon-expressing pancreatic α cells. This will provide a simple and efficient method to produce functionally competent cells for therapeutic regenerative medicine.