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. 2020 Sep 1;9:14. doi: 10.1186/s13619-020-00053-5

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© The Author(s) 2020

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Current models of intestinal epithelium during homeostasis and regeneration. a During homeostasis, multipotent Lgr5⁺ ISCs maintain regular epithelial renewal. The base-locate Lgr5⁺ ISCs generate rapidly proliferating TA cells and further differentiated into the various cell lineages. b Tissue injury that results in the loss of Lgr5⁺ ISCs drives a regenerative response to recover the Lgr5⁺ ISC pool. Left: the reserve stem cell model: damage-resistant + 4 quiescent stem cells function as the “reserve stem cells” to refill the Lgr5⁺ pool and restore the epithelial architecture. Right: the dedifferentiation model: acute damages result in the loss of the Lgr5⁺ cells and trigger dedifferentiation of progenitors and mature cells to replenish the Lgr5⁺ ISC population