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New platform of high efficiency iPSC reprogramming

 

Induced pluripotent stem cells (iPSCs), which can be generated by reprogrammed somatic cells, provides a model for investigating cell developmental processes. Generation of iPSCs by somatic cells usually goes through the enforced expression of transcription factors including Oct4, Klf4, Sox2, and c-Myc. In a recent study published on Stem Cell Reports, Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming of different differentiated cells.

 

In the study, >80% mouse embryonic fibroblasts (MEFs) reprogrammed to iPSCs by inhibiting TGF-β together with activating Wnt signaling, in the presence of an enzymatic cofactor, ascorbic acid (AA). Reprogramming took only 1 week to reach this high efficiency. On the other hand, hepatoblasts and granulocyte-macrophage progenitors (GMPs), two progenitors, required only TGF-β inhibition or Wnt activation, respectively, to rapidly trigger pluripotency loci and to enter a pluripotent state. The reprogram processes were closed to 100% efficiency in less than a week. By further investigation, researchers suspected specific molecular features are responsible for the differences between fibroblasts and progenitor cells.

 

Collectively, the results reveal specific requirements of different somatic cells in process of iPSCs generation, as well as, provide a rapid and efficient platform for further investigating the mechanism of pluripotency induction.

 

Reference:
Stem Cell Reports. 2014 Oct 14;3(4):574-584.

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Wnt/beta-catenin GSK-3 TGF-beta/Smad