Periodic Reporting for period 1 - LIVERZAP (Live, In vivo Visualisation of liver Regeneration in Zebrafish After Photoablation of hepatocytes)
Período documentado: 2018-01-01 hasta 2019-12-31
(1) Yanger, K. et al.(2014) “Adult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation.” Cell Stem Cell,15: 340–349.
(2) Miyaoka, Y. et al. (2012) “Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration.” Current Biology,22: 1166–1175.
(3) Español Suñer, R. et al. (2012) “Liver Progenitor Cells Yield Functional Hepatocytes in Response to Chronic Liver Injury in Mice.” Gastroenterology,143: 1564–1575.
(4) Zheng, D. et al. (2006) “Oval Cell Response in 2-Acetylaminofluorene/Partial Hepatectomy Rat Is Attenuated by Short Interfering RNA Targeted to Stromal Cell-Derived Factor-1.” The American Journal of Pathology,169: 2066–2074
The extent of injury can be accurately controlled using light and hence can also be performed within a high-resolution microscope. In the project, a novel light-sheet microscopy approach was developed to visualise the cellular morphodynamics of the hepatic regenerative response in real-time after LIVERZAP-mediated liver damage. Detailed analysis of the time-lapse imaging data was performed by tracking of biliary epithelial cell (BEC) nuclei. These data revealed that both active migration and passive tissue growth contribute to liver regeneration. Bulk RNA-sequencing of hepatocytes and BECs has been performed. After in depth analysis and comparison to other published data sets, these data will be used to add mechanistic detail to the role of these regenerative cell behaviours.
A manuscript is currently being written to disseminate the results of the LIVERZAP project. Furthermore, the fellow has actively presented the work at several regional and international scientific conferences including the Annual Spring Meeting of the British Society for Developmental Biology (2019) and the Copenhagen Bioscience Conference, The Stem Cell Niche (2018). The fellow has taken part in a collaborative art-science dissemination project SciVi (http://www.scivi.dk/) with a view to publicising the research output of LIVERZAP to the lay public. Together with Berlin-based illustrator and live-painter Cosimo Miorelli , a short, animated video (or rather, a “speed-painted” video) of about 3.5 minutes will be produced (pending funding) to:
- present the practices of this specific research
- briefly explain how the liver works and why is it important
- show how the liver reacts to damage and regenerates (main focus of this research and of this video).
(5) He, J., et al. (2016) “A genetically targetable near-infrared photosensitizer.” Nature Methods, 13:263–268
(6) Lu, W.-Y. et al. (2015) “Hepatic progenitor cells of biliary origin with liver repopulation capacity.” Nature cell biology,17: 971–983.
(7) Choi, T.-Y. et al. (2014) “Extensive Conversionof Hepatic Biliary Epithelial Cells to Hepatocytes After Near Total Loss of Hepatocytes in Zebrafish.” Gastroenterology,146: 776–788