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i PSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type.
The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors Oct4 (Pou5f1), Sox2, c Myc, and Klf4.
Further, because embryonic stem cells can only be derived from embryos, it has so far not been feasible to create patient-matched embryonic stem cell lines.
Since i PSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line.
The table at right summarizes the key strategies and techniques used to develop i PS cells in the first five years after Yamanaka et al.'s 2006 breakthrough.
Rows of similar colors represent studies that used similar strategies for reprogramming.
While this combination is most conventional in producing i PSCs, each of the factors can be functionally replaced by related transcription factors, mi RNAs, small molecules, or even non-related genes such as lineage specifiers.
Similar to ESCs, these i PSCs had unlimited self-renewal and were pluripotent, contributing to lineages from all three germ layers in the context of embryoid bodies, teratomas, and fetal chimeras.
However, considerable advances have been made in improving the efficiency and the time it takes to obtain i PSCs.
Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.
However, instead of using Fbx15 to select for pluripotent cells, the researchers used Nanog, a gene that is functionally important in ESCs.
By using this different strategy, the researchers created i PSCs that were functionally identical to ESCs.
Reprogramming of human cells to i PSCs was reported in November 2007 by two independent research groups: Shinya Yamanaka of Kyoto University, Japan, who pioneered the original i PSC method, and James Thomson of University of Wisconsin-Madison who was the first to derive human embryonic stem cells.