Induced Pluripotent Stem Cells (iPSCs) BT - Induced Pluripotent Stem Cells

Abstract

Takahashi and Yamanaka showed that overexpression of defined transcription factors can also convert cells (or nuclei) to pluripotent state. The idea was the factors that maintain pluripotency in ESCs might induce pluripotency in somatic cells. They tested 24 transcription factors on the basis of their important roles in mESCs. They introduced combinations of those genes into mouse fibroblasts through retroviral transduction. The cells were carrying an antibiotic-resistance gene that would only be expressed when F-box protein 15 gene (Fboxo15) was turned on. They designed this experiment so that this antibiotic-resistance gene could also be turned on if pluripotency was induced by the combination of 24 candidate genes. Surprisingly they found that only four of these factors were sufficient to generate ESC-like colonies. The combination of genes was octamer 3/4 (Oct4, also known as Pou5f1), SRY box–containing gene 2 (Sox2), Kruppel-like factor 4 (Klf4) and c-Myc (later called OKSM). These reprogrammed cells were called as induced pluripotent stem cells (iPSCs).