Somatic to iPS Cell Reprogramming

Somatic cells can be reprogrammed by artificially introducing genes for four transcription factors – Oct4, Sox2, Klf4, and c-Myc. These genes are separately transferred into the cells using viral vectors.

When the genes integrate into the genome, these transcription factors are expressed. They further change the cell’s gene expression pattern to activate cell growth, alter metabolism, and remodel the cytoskeleton.

c-Myc activates genes to promote cell proliferation; it also helps reorganize the chromatin to allow the other three transcription factors to bind and regulate genes required for pluripotency.

Klf4 forms a complex with Oct4 and Sox2 to activate the expression of Nanog–a transcription factor required for self-renewal. Additionally, Klf4 represses specific genes involved in cell senescence, further maintaining pluripotency.

Oct4, Sox2, and Nanog are the core transcription factors that regulate more than 300 genes, including those responsible for metabolic changes and cytoskeletal reorganization– events that transform cells over several generations into pluripotent ones.