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. 2021 Oct 26;13(10):1564–1579. doi: 10.4252/wjsc.v13.i10.1564

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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/

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Niche microenvironment of intestinal stem cells at the crypt bottom. Bidirectional gradients of biochemical signals established by neighboring cells including Paneth cells, subepithelial cells and enterocytes regulate the self-renewal and differentiation of intestinal stem cells synergistically. TGF-β: Transforming growth factor-β; TGF-α: transforming growth factor-α; EGF: Epidermal growth factor; EGFR: Epidermal growth factor receptor; IGF: insulin-like growth factor; BMPR: Bone morphogenetic protein receptor; BMP: Bone morphogenetic protein; DKK1: Dickkkopf-1; Dll1/4: Delta-like 1/4.