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Lineage conversion methodologies meet the reprogramming toolbox

Nature Cell Biology volume 14, pages 892–899 (2012)Cite this article

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Lineage conversion has recently attracted increasing attention as a potential alternative to the directed differentiation of pluripotent cells to obtain cells of a given lineage. Different means allowing for cell identity switch have been reported. Lineage conversion relied initially on the discovery of specific transcription factors generally enriched and characteristic of the target cell, and their forced expression in cells of a different fate. This approach has been successful in various cases, from cells of the hematopoietic systems to neurons and cardiomyocytes. Furthermore, recent reports have suggested the possibility of establishing a general lineage conversion approach bypassing pluripotency. This requires a first phase of epigenetic erasure achieved by short overexpression of the factors used to reprogram cells to a pluripotent state (such as a combination of Sox2, Klf4, c-Myc and Oct4), followed by exposure to specific developmental cues. Here we present these different direct conversion methodologies and discuss their potential as alternatives to using induced pluripotent stem cells and differentiation protocols to generate cell populations of a given fate.

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Figure 1: Reprogramming strategies allowing for the generation of specific cell types.
Figure 2: Direct lineage conversion as a suitable approach for the generation of specific cell types.
Figure 3: Indirect lineage conversion allows for a more general approach in the absence of specific transcription factors.

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Acknowledgements

We would like to thank Emmanuel Nivet for critical discussions on the manuscript. We also thank May Schwarz and Ilir Dubova for administrative support. We apologize to all our colleagues whose work could not be discussed due to space limitations. S.H.B was supported by Creative Research Initiative Program (Research Center for Chromatin Dynamics, 2009-0081563). Work in the laboratory of JCIB was supported by grants from Fundacion Cellex, the G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi, the California Institute of Regenerative Medicine and MINECO.

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  1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA

    Ignacio Sancho-Martinez & Juan Carlos Izpisua Belmonte

  2. Department of Biological Sciences, Chromatin Dynamics Research Center, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea

    Sung Hee Baek

  3. Center of Regenerative Medicine in Barcelona, Doctor Aiguader 88, Barcelona, 08003, Spain

    Juan Carlos Izpisua Belmonte

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Sancho-Martinez, I., Baek, S. & Izpisua Belmonte, J. Lineage conversion methodologies meet the reprogramming toolbox. Nat Cell Biol 14, 892–899 (2012). https://doi.org/10.1038/ncb2567

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