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Spotlight on Stem Cells

Toward a new paradigm of cell plasticity

Leukemia volume 16, pages 542–548 (2002)Cite this article

Abstract

The standard paradigm of embryologic development and adult tissue reconstitution posits unidirectional, hierarchical lineages. The presumed mechanisms underlying these differentiative pathways are gene restrictions, such as methylation and heterochromatin formation, which are commonly described as irreversible. However, recent discoveries regarding multi-organ stem cells demonstrate that ‘true plasticity’ exists, with cells of one organ turning into cells of other organs, including differentiative transformations that cross barriers between tissues derived from different primitive germ layers. These findings, along with earlier experiments into heterokaryon formation and longstanding recognition of reactive and neoplastic lesions in humans and animals, suggest that lineage pathways are not, in fact, unidirectional. Moreover, physiologic mechanisms of reversal of gene restrictions have been recognized. Therefore, in response to these observations, we suggest a new paradigm of cell plasticity, elucidating three guiding principles of ‘genomic completeness’, ‘uncertainty of cell characterization’, and ‘stochastic nature of cell origins and fates’. These principles imply a change in the way data can be interpreted and could alter subsequent hypothesis formation. This new paradigm will hopefully lead us forward to a more flexible and creative exploration of the potential of adult vertebrate cells.

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Acknowledgements

This material was first presented at a ‘Focused Workshop on Stem Cell Plasticity’, held in Santa Barbara CA, May 3–6, 2001, sponsored by The Leukemia and Lymphoma Society (White Plains, NY) with the help of the Great Basin Medical Research Foundation (Reno, NV). The proceedings of that meeting were published in Blood, Cells, Molecules, and Diseases, May–June 2001. This article represents the expanded form of that original presentation. The authors would like to thank Drs Rebecca Wells, Paula Vertino, Cindy Loomis, A Brian West, Rachel Brody and Vittorio Defendi for their helpful contributions, including thoughtful discussions and reviews of the manuscript. We are grateful for their receptivity to new ideas, patient teaching, and creative imaginations.

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Authors and Affiliations

  1. Department of Pathology, New York University School of Medicine, New York, NY, USA

    ND Theise

  2. Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA

    DS Krause

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Theise, N., Krause, D. Toward a new paradigm of cell plasticity. Leukemia 16, 542–548 (2002). https://doi.org/10.1038/sj.leu.2402445

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