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. 2020 Mar 18;11:1429. doi: 10.1038/s41467-020-15258-0

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Structure of the stratified squamous epithelia from the interfollicular epidermis (skin) and esophagus of adult mice. Proliferating keratinocytes are located in the basal layer. Upon differentiation they migrate through suprabasal layers until they are ultimately lost by shedding. A balance should be established between cell division and cell loss to guarantee tissue homeostasis. HF, hair follicle; SG, sebaceous gland. b Rationale of genetic lineage tracing. Low-dose induction in transgenic mice allows recombination and conditional labeling of punctuated keratinocyte progenitors in the basal layer. These cells and their progeny remain labeled and can be tracked to study clonal dynamics over time. c Rationale of Histone 2B-GFP (H2BGFP) dilution experiments (a top-down view of the basal-layer plane is sketched). Transgenic-mouse keratinocytes express H2BGFP protein while on doxycycline (Dox) treatment. After Dox withdrawal cycling cells dilute their H2BGFP content with every division, allowing to study cell-proliferation rate. d Different stochastic cell-proliferation models invoked to explain epithelial self-renewal. Branches reflect different possible fates for a given proliferating cell upon division. SP: single-progenitor model. 2xSC: two stem-cell model, involving two independent types of proliferating cells dividing at different rates. SC-CP: stem cell-committed progenitor model, involving slow-cycling stem cells underpinning a second population of quickly-dividing progenitors.