Hankeova, Simona; Salplachta, Jakub; Zikmund, Tomas; Kavkova, Michaela; Van Hul, Noémi; Brinek, Adam; Smekalova, Veronika; Laznovsky, Jakub; Dawit, Feven; Jaros, Josef; Bryja, Vítězslav; Lendahl, Urban
Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.
Work in ERA lab is supported by the Swedish Research Council, the Center of Innovative Medicine (CIMED) Grant, Karolinska Institutet, and the Heart and Lung Foundation, and the Daniel Alagille Award from the European Association for the Study of the Liver. One project in ERA lab is funded by ModeRNA, unrelated to this project. The funders have no role in the design or interpretation of the work. SH has been supported by a KI-MU PhD student program, and by a Wera Ekstro¨m Foundation Scholarship. We are grateful for support from Tornspiran foundation to NVH. JK: This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II and CzechNanoLab Research Infrastructure supported by MEYS CR (LM2018110) . UL: The financial support from the Swedish Research Council and ICMC (Integrated CardioMetabolic Center) is acknowledged. JJ: The work was supported by the Grant Agency of Masaryk University (project no. MUNI/A/1565/2018). We thank Kari Huppert and Stacey Huppert for their expertise and help regarding bile duct cannulation and their laboratory hospitality. We also thank Nadja Schultz and Charlotte L Mattsson for their help with common bile duct cannulation. We thank Daniel Holl for his help with trachea cannulation. We thank Nikos Papadogiannakis for his assistance with mild Alagille biopsy samples and discussion. We thank Karolinska Biomedicum Imaging Core, especially Shigeaki Kanatani for his help with image analysis. We thank Jan Masek and Carolina Gutierrez for their scientific input in manuscript writing. We thank Peter Ranefall and the BioImage Informatics (SciLife national facility) for their help writing parts of the MATLAB pipeline. The TROMA-III antibody developed by Rolf Kemler was obtained from the Developmental Studies Hybridoma (DSHB) Bank developed under the auspices of NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA52242. We thank Goncalo M Brito for all illustrations. This work was supported by the European Union (European Research Council Starting grant 851288 to E.H.).
Hankeova S, Salplachta J, Zikmund T, et al. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. eLife. 2021;10. doi:10.7554/eLife.60916
Hankeova, S., Salplachta, J., Zikmund, T., Kavkova, M., Van Hul, N., Brinek, A., … Andersson, E. R. (2021). DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.60916
Hankeova, Simona, Jakub Salplachta, Tomas Zikmund, Michaela Kavkova, Noémi Van Hul, Adam Brinek, Veronika Smekalova, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.60916.
S. Hankeova et al., “DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome,” eLife, vol. 10. eLife Sciences Publications, 2021.
Hankeova S, Salplachta J, Zikmund T, Kavkova M, Van Hul N, Brinek A, Smekalova V, Laznovsky J, Dawit F, Jaros J, Bryja V, Lendahl U, Ellis E, Nemeth A, Fischler B, Hannezo EB, Kaiser J, Andersson ER. 2021. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. eLife. 10, e60916.
Hankeova, Simona, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” ELife, vol. 10, e60916, eLife Sciences Publications, 2021, doi:10.7554/eLife.60916.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):
2021_eLife_Hankeova.pdf 9.26 MB