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Nature Reviews Molecular Cell Biology
  • Review Article
  • Published:

How cells change their phenotype

Nature Reviews Molecular Cell Biologyvolume 3, pages187–194 (2002)Cite this article

Key Points

  • The terms 'metaplasia' and 'transdifferentiation' are defined. Metaplasia is the conversion of one cell or tissue type into another and transdifferentiation (a subset of metaplasia) is the conversion of one differentiated cell type to another, with or without an intervening cell division. Methods for proving their occurrence are described.

  • Examples are presented of bone-marrow-derived stem cells that give rise to cells of completely different embryonic lineages following transplantation.

  • Purified haematopoietic stem cells have been shown to convert to liver cells or to cells of the central nervous system.

  • Well-characterized examples of transdifferentiation include conversion of pancreas to liver, myoblasts to adipocytes and iris to lens.

  • Metaplasias arise by switching of the state of key developmental control genes, some of which have been identified.

  • It remains unclear whether the marked cell-type changes of grafted bone-marrow cells reflect a role for these cells in normal renewal of all tissues, or whether it is a rare phenomenon at the cellular level that is associated with the irradiation of the hosts.

Abstract

Recent attention has focused on the remarkable ability of adult stem cells to produce differentiated cells from embryologically unrelated tissues. This phenomenon is an example of metaplasia and shows that embryological commitments can be reversed or erased under certain circumstances. In some cases, even fully differentiated cells can change their phenotype (transdifferentiation). This review examines recently discovered cases of metaplasia, and speculates on the potential molecular and cellular mechanisms that underlie the switches, and their significance to developmental biology and medicine.

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Figure 1: Stem cells can undergo self-renewal and generate transit cells and, finally, differentiated cells.
Figure 2: Transdifferentiation of hepatocytes from pancreatic exocrine cells.
Figure 3: A theoretical model for the occurrence of transdifferentiation.
Figure 4: The Cre/lox system can be used for lineage analysis.

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Acknowledgements

We apologize to the many colleagues whose work is not discussed owing to space limitations. The research in the authors' labs is supported by the Medical Research Council and Wellcome Trust.

Author information

Authors and Affiliations

  1. Department of Biology and Biochemistry, Developmental Biology Programme, University of Bath, Bath, BA2 7AY, UK

    David Tosh & Jonathan M. W. Slack

Authors
  1. David Tosh

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  2. Jonathan M. W. Slack

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Corresponding author

Correspondence toDavid Tosh.

Glossary

METAPLASIA

The conversion of one cell or tissue type into another. Includes transdifferentiation and also conversion between undifferentiated stem cells of different tissues.

STEM CELL

A cell that has the potential to divide and produce a replica cell as well as differentiated progeny.

DIFFERENTIATION

The synthesis of proteins that are produced selectively in a single cell type (for example, albumin in hepatocytes). Differentiation is generally reflected in specialized structure (such as bile canaliculi) and function (such as synthesis of bile).

EPIGENETIC CHANGE

A sTable change in phenotype that arises from processes other than the alteration of sequences of bases in genomic DNA.

DYSPLASIA

A cellular growth abnormality in which the cellular appearance is altered and tissue architecture might be disturbed.

HOMEOTIC MUTATIONS

A class of mutations in which a given tissue or body part develops in the same way as one that is normally present in another part of the body.

IMAGINAL DISCS

Single-cell layer epithelial structures of theDrosophila larva that give rise to wings, legs and other appendages.

DETERMINATION

The irreversible commitment of a cell to follow a pathway of development.

CRE/lox

A site-specific recombination system derived fromEscherichia coli bacteriophage P1. Two short DNA sequences (lox sites) are engineered to flank the target DNA. Activation of the Cre-recombinase enzyme catalyses recombination between thelox sites, leading to excision of the intervening sequence.

5′ BROMODEOXYURIDINE

A base analogue of thymidine, which is often used experimentally to label dividing cells.

COMMITMENT

The intrinsic nature of a cell to follow a pathway of development.

CHONDROCYTE

A differentiated cell of cartilage tissue.

OSTEOBLAST

A mesenchymal cell with the capacity to differentiate into bone tissue.

HEREDITARY TYROSINAEMIA TYPE I

An autosomal recessive condition caused by mutation of theFAH gene. Patients have increased levels of tyrosine in the blood, and symptoms include deterioration of the liver and accumulation of other amino acids, such as methionine in the blood and urine.

PARENCHYMAL TISSUE

All tissue other than lymphoid tissue. Lymphoid tissue is derived from the bone marrow, whereas parenchymal tissue is not.

ASTROCYTE

A star-shaped glial cell that supports the tissue of the central nervous system.

OLIGODENDROCYTE

A glial cell in the nervous system that forms a myelin sheath around axons.

MICROGLIA

Phagocytic immune cells in the brain that engulf and remove cells that have undergone apoptosis.

ECTODERM

The outermost germ layer of the developing embryo. It gives rise to the epidermis and the nerves.

PURKINJE CELLS

Large, pear-shaped cells of the cerebellum, which are connected to multi-branched nerve cells that cross the cerebellar cortex.

ENDODERM

The innermost germ layer of the developing embryo. It gives rise to the epithelia of the lung, digestive tract, bladder and urethra.

PLURIPOTENCY

A pluripotent stem cell can give rise to more than one differentiated cell type.

GLIAL CELLS

Non-neuronal cells of the central nervous system, which comprise astrocytes, oligodendrocytes, microglia and ependymal cells.

SPECIFICATION

A labile form of commitment, which can be altered by environmental signals.

MESODERM

The middle germ layer of the developing embryo. It gives rise to the musculoskeletal, vascular and urinogenital systems, and to connective tissue (including that of the dermis).

TROPHOBLAST

The surface cell layers of an embryo at the blastocyst stage.

HETEROTOPIAS

A misplaced tissue, which arises during embryogenesis.

INTERCALARY REGENERATION

Regeneration that occurs at a junction between experimentally joined body parts, which results in the re-formation of parts that normally lie between them.

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