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. 2021 Mar 12;12:1659. doi: 10.1038/s41467-021-21801-4

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© The Author(s) 2021

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. 2 — a Connected component of the reconstructed GRN of induced pluripotent stem cells. Enhancer and promoter regulation (green) is distinguished from enhancer-only regulation (blue). The size of the nodes (gold) is proportional to the number of regulated TFs. b Predicted conversion efficiency for inducing PSCs from hematopoietic stem cells (HSC, red), normal human dermal fibroblasts (NHDF, green), embryonic fibroblasts (blue), neural stem cells (NSC, orange), keratinocytes (purple), and melanocytes (gold). For each conversion, two experimentally validated combinations of IFs were compared. The predicted score of the combinations with the lower experimental efficiency is divided by the predicted score of the combination with the higher experimental efficiency and colored depending on the initial cell type. Each small square in a grid corresponds to 1%. (O = POU5F1, S = SOX2, K = KLF4, M = MYC) c Model simulations of 1000 random perturbations of NHDF cells that do not contain POU5F1 for 200 simulation steps. The color code represents the amount of dissimilarity with yellow representing maximum dissimilarity and red depicting perfect agreement. The similarity is measured as the number of expressed TFs in the iPSC network during the simulation. The iPSC network corresponds to dissimilarity of 0 (red) and cannot be induced without POU5F1 being expressed. d Comparison of EpCAM-positive cells (left) and predicted scores by IRENE (right) when iPSC differentiation towards mammary epithelial cells is induced with 5- (orange, red) or 6 (blue, green) TF combinations. The median is represented by a solid line within the boxes. The lower and upper bounds of boxes are the first and third quartile, respectively. Whiskers extend to 1.5-times interquartile range or the minimum/maximum value. n = 4 (6 TFs) and 5 (5 TFs) independent experiments. e.g., Comparison of scores predicted by IRENE with the percentage of successfully differentiated e mammary epithelial cells (blue) f melanocytes (red) and g NK cells (green).