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. 2023 Nov 3;20(1):25–51. doi: 10.1007/s12015-023-10647-6

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© The Author(s) 2023

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 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/.

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Fig. 1 — CD133 regulation in hypoxic conditions. Hypoxia-inducible Factors (HIFs) 1/2α upregulate the levels of Sox2 and Oct4, and also epigenetic regulators such as ATAD2 that favor gene transcription. HIF1α can stabilize NICD (Notch intracellular domain) in the nucleus and promote NICD/CSL transcriptional activity leading to improve CD133 expression as well as promoting Hedgehog signaling through improved Shh ligand. Also, hypoxia can promote β-catenin stabilization via increased glycolysis and lactate release leading to β-catenin nuclear translocation and CD133 expression. Created with BioRender.com