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16.06.16 New model for stem cell self-renewal emphasises reversible states

last modified Jun 21, 2016 04:41 PM
Ben Simons and Philip Greulich show that a model in which stem cells exhibit ‘dynamic heterogeneity’ can robustly explain patterns of self-renewal and differentiation, contributing to our understanding of tissue maintenance.
16.06.16 New model for stem cell self-renewal emphasises reversible states

Illustration of the dynamic heterogeneity model dynamics on a 2D lattice

Dynamic heterogeneity as a strategy of stem cell self-renewal

Greulich P and Simons BD (2016) Proc Natl Acad Sci U S A. DOI 10.1073/pnas.1602779113 [Epub ahead of print] PMID: 27313213

Abstract

To maintain cycling adult tissue in homeostasis the balance between proliferation and differentiation of stem cells needs to be precisely regulated. To investigate how stem cells achieve perfect self-renewal, emphasis has been placed on models in which stem cells progress sequentially through a one-way proliferative hierarchy. However, investigations of tissue regeneration have revealed a surprising degree of flexibility, with cells normally committed to differentiation able to recover stem cell competence following injury.

Here, we investigate whether the reversible transfer of cells between states poised for proliferation or differentiation may provide a viable mechanism for a heterogeneous stem cell population to maintain homeostasis even under normal physiological conditions. By addressing the clonal dynamics, we show that such models of “dynamic heterogeneity” may be equally capable of describing the results of recent lineage tracing assays involving epithelial tissues. Moreover, together with competition for limited niche access, such models may provide a mechanism to render tissue homeostasis robust. In particular, in 2D epithelial layers, we show that the mechanism of dynamic heterogeneity avoids some pathological dependencies that undermine models based on a hierarchical stem/progenitor organization.

 

More about the Simons lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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