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Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration

Nature Reviews Molecular Cell Biology volume 12, pages 79–89 (2011)Cite this article

Subjects

Key Points

  • The ultimate goal of regenerative medicine is to replace lost or damaged cells. This can potentially be accomplished using the processes of dedifferentiation, transdifferentiation or reprogramming.

  • During dedifferentiation, a terminally differentiated cell reverts back to a less-differentiated stage from within its own lineage, which allows it to proliferate. Many regenerative processes have been associated with dedifferentiation.

  • Transdifferentiation sees cells regress to a point when they can switch lineages or can also occur directly between two different cell types.

  • Reprogramming aims to induce differentiated cells into reverting to pluripotency. From here, they can differentiate into almost any cell type.

  • During dedifferentiation and transdifferentiation, well-defined intermediate cell types have been identified. The process of reprogramming seems to be largely stochastic.

  • Dedifferentiation and transdifferentiation can be successfully achieved in vivo, and reprogramming facilitates genetic manipulation such as correcting disease-inducing mutations.

Abstract

The ultimate goal of regenerative medicine is to replace lost or damaged cells. This can potentially be accomplished using the processes of dedifferentiation, transdifferentiation or reprogramming. Recent advances have shown that the addition of a group of genes can not only restore pluripotency in a fully differentiated cell state (reprogramming) but can also induce the cell to proliferate (dedifferentiation) or even switch to another cell type (transdifferentiation). Current research aims to understand how these processes work and to eventually harness them for use in regenerative medicine.

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Figure 1: Overview of reprogramming, transdifferentiation and dedifferentiation.
Figure 2: Natural dedifferentiation during zebrafish heart regeneration.
Figure 3: Natural and artificial transdifferentiation.
Figure 4: The induction of pluripotency.

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Acknowledgements

We apologize to our colleagues whose research could not be included in this article owing to size limitations. We thank A. Faucherre and M. J. Barrero for constructive criticism of the manuscript and the members of the laboratory for discussions. Work in the laboratory of J.C.I.B. was supported by grants from MICINN, Fundacion Cellex, Sanofi-Aventis and the G. Harold and Leila Y. Mathers Charitable Foundation.

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  1. Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003, Barcelona, Spain

    Chris Jopling, Stephanie Boue & Juan Carlos Izpisua Belmonte

  2. Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA

    Juan Carlos Izpisua Belmonte

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Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration

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Glossary

Pluripotency

The ability of a cell to give rise to all cells of the embryo. Cells of the inner cell mass and its derivative embryonic stem cells are pluripotent.

Totipotent

Pertaining to the ability of a cell to give rise to all cells of an organism, including embryonic and extra-embryonic tissues. Zygotes are totipotent.

Hyperplasia

Growth that is due to an increase in the number of cells.

Hypertrophic growth

Growth that is due to an increase in the size of cells.

Multipotent

Pertaining to the ability of a cell to give rise to different cell types of a given cell lineage. Most adult stem cells, such as gut stem cells, skin stem cells, haematopoietic stem cells and neural stem cells, are multipotent.

Schwann cell

A cell type that wraps around the axons of peripheral nerves and forms the insulating myelin sheath.

Neural crest cell

A cell type that migrates during neurulation and forms most of the peripheral nervous system (and many other structures) in the embryo.

Myotube

An elongated multinucleate cell (with three or more nuclei) that contains some peripherally located myofibrils. Myotubes are formed in vivo or in vitro by the fusion of myoblasts; they eventually develop into mature muscle fibres that have peripherally located nuclei and most of their cytoplasm filled with myofibrils.

β-cell

A cell type in the pancreas, found in the islets of Langerhans, that produces insulin.

Pancreatic exocrine cell

A pancreatic cell type that is responsible for the secretion of bicarbonate ions and digestive enzymes.

DNA methyltransferase

An enzyme that catalyses the addition of a methyl group to C or A. DNMT1 is a maintenance DNA methyltransferase, DNMT3a and DNMT3b are de novo DNA methyltransferases.

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Jopling, C., Boue, S. & Belmonte, J. Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol 12, 79–89 (2011). https://doi.org/10.1038/nrm3043

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