A Transcriptional Roadmap to the Induction of Pluripotency in Somatic Cells

作者：Wang Ying; Mah Nancy; Prigione Alessandro; Wolfrum Katharina; Andrade Navarro Miguel A; Adjaye James^*

来源：Stem Cell Reviews, 2010, 6(2): 282-296.

DOI：10.1007/s12015-010-9137-2

• Cellular reprogramming
• EMT
• MET
• Gene regulatory networks
• iPS cells
• ES cells
• PiPSC
• Self-renewal
• Pluripotency

Human embryonic stem (ES) cells possess an enormous potential for applications in regenerative medicine. However, these cells have several inevitable hurdles limiting their clinical applications, such as transplant rejection and embryo destruction. A milestone recently achieved was the derivation of induced pluripotent stem (iPS) cells by over-expressing combinations of defined transcription factors, namely, OCT4, SOX2, NANOG, and LIN28 or OCT4, SOX2, KLF4, and c-MYC. Human iPS cells exhibit many characteristics identical to those of inner cell mass-derived ES cells. Here, we summarize the generation of human fibroblast-derived iPS cells and discuss the promises and limitations of their use. In addition, by utilising numerous published transcriptome datasets related to ES cells, fibroblast-derived iPS cells, partially induced pluripotent stem cells (PiPSC) and wild type fibroblasts, we reveal similarities (self-renewal signature) and differences (donor cell-type and PiPSC signatures) in genes and associated signaling pathways operative in the induction of pluripotency in fibroblasts. In particular, we highlight that induction of ground state pluripotency is also favoured by the inhibition of epithelial mesenchymal transition (EMT) and hence the induction of mesenchymal epithelial transition (MET). We anticipate that these findings might aid in the establishment of more efficient protocols for inducing pluripotency in somatic cells.

• 出版日期2010-6