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. 2018 Jun 12;8:8977. doi: 10.1038/s41598-018-27119-4

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© The Author(s) 2018

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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Schema of proposed DCN action on stem cell hierarchy. Figure 9 summarizes the DCN effects on stem cell self-renewal and differentiation: inhibition of self-renewal of ES-like cells (reduced spheroid numbers); promotion of ES differentiation to TS-like cells (increased TS markers); promotion of self-renewal of TS-like cells (increased second generation spheroid forming efficiency); inhibition of differentiation of TS-like cells to villous (syncytium formation) and EVT pathways (marker expression).