AsianScientist (Jun. 4, 2013) – Sequential introduction of reprogramming proteins leads to a greater number of cells being reprogrammed to pluripotent, embryonic-like state than when using a simultaneous introduction method, says a new study.
Ever since Shinya Yamanaka first reprogrammed mice and human adult cells into induced pluripotent stem cells (iPSCs) using a cocktail of four protein transcription factors (Oct3/4, Sox2, Klf4, c-Myc), scientists have been attempting to develop new techniques to make iPSC production safer and more high yielding. Present practices for reprogramming somatic cells to induced pluripotent stem cells involve simultaneous introduction of reprogramming factors.
In this study, Duanqing Pei and colleagues from the Chinese Academy of Sciences in Beijing sequentially introduced the crucial four factors: Oct4–Klf4 first, then c-Myc and finally Sox2, and showed that sequential delivery outperformed simultaneous delivery. The increase in efficiency of reprogramming was observed both for mouse and human differentiated cells.
The team showed that the sequential protocol led to more efficient reprogramming: the cells more readily adopted mesenchymal characteristics before going through an epithelial state and finally reaching pluripotency. This process, called the epithelial-to-mesenchymal transition (EMT), is critical for cells to be reprogrammed to iPSCs.
This discovery, reported in Nature Cell Biology, provides a new technique that further optimizes the reprogramming of somatic cells to iPSCs.
The article can be found at: Liu X et al. (2013) Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT–MET mechanism for optimal reprogramming.
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