iPSC Research

iPSC Research

Shinya Yamanaka’s groundbreaking work on induced pluripotent stem cells (iPSCs) involved identifying a specific set of genes that could reprogram adult cells back into a pluripotent state. The genes initially used by Yamanaka were Oct3/4, Sox2, Klf4, and c-Myc, collectively known as the Yamanaka factors. Later research demonstrated that other combinations of genes could also induce pluripotency, but the original combination proved to be the most effective.

Oct3/4 (Octamer-binding transcription factor 3/4): Oct3/4 is a transcription factor essential for maintaining pluripotency in embryonic stem cells. It regulates the expression of genes involved in self-renewal and pluripotency and is crucial for reprogramming adult cells into a pluripotent state.
Sox2 (SRY (sex-determining region Y)-box 2): Sox2 is another transcription factor involved in maintaining pluripotency and self-renewal in embryonic stem cells. It interacts with Oct3/4 to regulate the expression of pluripotency-associated genes and plays a key role in reprogramming adult cells to an embryonic-like state.
Klf4 (Kruppel-like factor 4): Klf4 is a transcription factor that regulates various cellular processes, including proliferation, differentiation, and pluripotency. It functions in conjunction with Oct3/4 and Sox2 to reprogram adult cells into iPSCs.
c-Myc (cellular Myelocytomatosis oncogene): c-Myc is a proto-oncogene involved in the regulation of cell proliferation, growth, and apoptosis. Its role in reprogramming is to enhance the efficiency of iPSC generation, although its overexpression can also increase the risk of tumorigenesis.

These four transcription factors were introduced into adult somatic cells, such as fibroblasts, using viral vectors. Their expression led to the activation of pluripotency-associated genes and the induction of a pluripotent state resembling that of embryonic stem cells. Yamanaka’s discovery of these factors paved the way for the generation of patient-specific iPSCs, offering new possibilities for disease modeling, drug discovery, and regenerative medicine.