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. 2019 Dec 16;9:19162. doi: 10.1038/s41598-019-55631-8

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© The Author(s) 2019

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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Heme induces NRG-1 and reduces ERBB4 expression in the forebrain structures of human organoids (20 days in culture). Cortical organoids were treated with heme for 8 hours, and NRG-1 was then added for 18 hours. The results showed that, compared to no treatment (a), heme induced NRG-1 expression. (b) The addition of NRG-1 to the treatment reduced its endogenous expression due to an improvement in cell injury. (c) ERBB4 expression decreased with heme treatment (e) compared to no treatment. (d) The addition of NRG-1 increased the levels of ERBB4 (f) compared to that induced by heme alone (e) but not compared to basal levels. (d) Scale bar: 20 µm.