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Stem cells

Splitting up differentiation and cell cycle exit

Nature Cell Biology volume 24, pages 1687–1688 (2022)Cite this article

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The onset of differentiation has been assumed to follow withdrawal from the cell cycle. A new study shows that keratinocytes initiate differentiation before exiting the cell cycle, allowing the skin to respond rapidly to damage.

Many cell types with specialized functions, such as leukocytes, erythrocytes, enterocytes and the keratinocytes that cover the skin, have lost the ability to divide and are referred to as terminally differentiated. Maintaining these cells requires dedicated progenitor populations, which continually replace terminally differentiated cells as they are lost by processes such as apoptosis or being shed from epithelia. In the skin, which consists of layers of keratinocytes, cells are shed from the surface and replaced by progenitors in the lowest, basal cell layer. Progenitor divisions generate either two progenitor daughters, two differentiating daughters or one cell of each type. Large-scale, long-term genetic lineage tracing of a representative sample of progenitors indicates the likelihood of each division outcome is balanced, so that, averaged out over the entire population, progenitor divisions result in 50% progenitor daughters and 50% cells that go on to differentiate1. The differentiating cells leave the basal layer and eventually migrate to the tissue surface, so that the tissue is maintained. Although revealing long-term average cell behaviour, such studies give no insight into the cell state transitions that occur during the process of differentiation. Key questions, such as when differentiation begins and whether differentiation is linked to cell cycle exit, remain open. In this issue of Nature Cell Biology, Cockburn et al. show that keratinocyte differentiation is initiated much earlier than previously thought and that differentiating cells may complete a further round of cell division2.

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Fig. 1: Proposed model of epidermal basal cell differentiation and the contribution of Krt10– and Krt10+ basal cells to tissue homeostasis.

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Acknowledgements

P.H.J. is supported by Wellcome Trust funding to the Sanger Institute (296194) and a Cancer Research UK Programme Grant (C609/A27326). A.H. is supported by a Maria Zambrano Grant to attract international talent from the Universitat de Barcelona and Ministerio de Universidades and co-funded with Next Generation EU funds.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain

    Albert Herms

  2. Cell Compartments and Signalling Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Albert Herms

  3. Wellcome Sanger Institute, Hinxton, UK

    Philip H. Jones

  4. Department of Oncology, University of Cambridge, Hutchison Research Centre, Cambridge Biomedical Campus, Cambridge, UK

    Philip H. Jones

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  1. Albert Herms
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  2. Philip H. Jones
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Correspondence to Philip H. Jones.

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Herms, A., Jones, P.H. Splitting up differentiation and cell cycle exit. Nat Cell Biol 24, 1687–1688 (2022). https://doi.org/10.1038/s41556-022-01022-7

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