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. 2018 Jul 23;26(5):826–842. doi: 10.1038/s41418-018-0157-9

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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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Fig. 8 — a Zygote is the beginning of embryonic differentiation. ESC in vitro comes from inner cell mass (ICM), which would development into gastrula with pluripotency gradually declined. Differentiation of ESC/iPSCs generates mesodermal characterized cells, including mesoderm progenitor and mesoderm. Epithelial–mesenchymal transition takes place in the development of gastrula. b ① Within 24 h UA could stimulate WNT pathway to increase beta- catenin and then promote EMT, downregulated E-cadherin and upregulated vimentin. ② UA could increase degradation of cyclinD1 in 48 h, which could decrease the expression of cyclinD1 and then lengthen G0/G1 phage. G0/G1 phage lengthened promoted differentiation