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. 2023 Dec 9;14:8159. doi: 10.1038/s41467-023-43795-x

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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 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. 7 — All the schematic representations in this figure were created with BioRender.com. A Schematic illustration: AGTR1-/- iPSCs were differentiated into kidney organoids and on day 7 of the differentiation protocol growing as a monolayer were transiently transduced with a lentivirus encoding a doxycycline (dox)-inducible hVEGF-A construct. Following aggregation (day 9), on day 12 and 13 of differentiation, organoids were treated with dox and transplanted under the kidney capsule of immunodeficient mice at day 14 (RV). B A representative bright field image of a Day 14 AGTR1-/- organoid exposed to Dox prior to transplantation under the kidney capsule of immunodeficient mice (left); and a representative image of a harvested kidney with engrafted day 14 Dox-treated AGTR1-/- organoid (right). C A representative Hematoxylin and Eosin (H&E) image of an explanted organoid showing kidney structures in the organoid 14 days after transplantation. D Immunofluorescence images of engrafted Dox-induced AGTR1-/- organoids. Wireframes are enlarged in (i, ii) at 40x magnification, sections from a different engrafted organoid are shown in the other frames. E Schematic representation of the experimental design for treatment of IC, ACE-/- and AGTR1-/- iPSC-derived organoids with 100 nM of AngII during differentiation until day 14, when media is collected and analyzed via an ELISA assay for secretion of VEGF-A. F Quantification of VEGF-A protein secretion in conditioned media of day 14 organoids derived from IC, ACE-/- or AGTR1-/- iPSCs either treated with 100 nM of AngII (AngII) or untreated (control). Results are presented as the mean ±S.E.M of n = 3 biologically independent experiments. Comparisons were performed using two-ways ANOVA. **p = 0.001, ****p < 0.0001. G Graphic summary of VEGF-A induction by AngII. H Graphic summary of our AGTR-/- engraftment rescue with pretreatment with hypoxia or VEGF-A, followed by schematic of hypothetical pathomechanism leading to PT paucity in RTD: delayed vasculogenesis with resultant nutrient deprivation impacts a critical time for PT development (RV =>SSB=>PT). Abbreviations: IC (Isogenic control), Dox- Doxycycline, AT1R- Angiotensin II receptor type 1 (protein), RV- Renal Vesicle, SSB- S-shaped bodies. Scale bar in all frames =100 µm. Source data for Fig. 7A are provided as a Source Data file.