H2020Индивидуална стипендия2018–2019

LIVERZAP · Live, In vivo Visualisation of liver Regeneration in Zebrafish After Photoablation of hepatocytes

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-01-01 → 2019-12-31
Финансиране от ЕС: 200 195 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Регенерацията на черния дроб при зебрните рибки се наблюдава в реално време чрез специална микроскопия след увреждане на клетките. Разбирането на тези процеси помага при търсенето на нови терапии за възстановяване на тъканите при хора.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Live, In vivo Visualisation of liver Regeneration in Zebrafish After Photoablation of hepatocytes

The liver is an essential metabolic organ with innate regenerative capacity. It has a complex tissue architecture that is crucially important for its function. In higher vertebrates, chronic liver disease and toxic insult leads to gradual compromise of the liver architecture through scarring and cirrhosis for which the only course of treatment is organ transplant. Development of novel therapies requires a detailed understanding of how the liver regenerates after injury in vivo. Prior to this project, studies using animal models of liver regeneration had revealed which hepatic cell types respond to different modes of damage (1-4). However, the cell behaviours and molecular signalling responsible for the restoration of the liver architecture following injury remained largely unclear and were yet to be studied in vivo. The LIVERZAP project pioneered real-time, in vivo image analysis and transcriptomics in zebrafish to examine and quantify the immediate cell behavioural response to liver injury. The fellow built on previous experience in microscopy to establish a deep tissue, multi-colour live imaging pipeline using light sheet microscopy. Cell-type specific molecular profiling provided by RNA-sequencing was employed to identify transcriptionally independent factors controlling the immediate morphogenetic response to liver injury. Together, the strategies employed by LIVERZAP have greatly enhanced the competencies of the fellow in specialized techniques, including state-of-the-art microscopy systems and methodologies, whilst providing excellent new tools for regeneration research. Fundamentally, the outcomes of LIVERZAP have begun to afford essential cellular and mechanistic insights into the restoration of liver architecture following injury, providing a platform for the long-term development of therapies for human liver pathologies. (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

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The specialised tissue architecture of the liver is crucially important for its essential metabolic functions in the body. The liver has the unique regenerative capacity to restore lost architecture when damaged. However, this remodelling process is compromised in chronic liver disease by scarring and cirrhosis. Often the only treatment is organ transplantation, thus the development of novel therapies is of vital importance. The necessary understanding of the dynamic cell rearrangement driving restoration of liver architecture has been limited by temporally static histological analyses of fixed regenerating tissue. Real-time monitoring of the mammalian liver is hindered by tissue opacity and deep organ position, whereas the surface location of the zebrafish liver and larval transparency makes this species uniquely suited for live, in vivo imaging of regeneration. LIVERZAP will generate a detailed map of the different cell behaviours driving restoration of liver architecture by pioneering real-time, in vivo imaging of regeneration in zebrafish. This will be achieved by: i) generating a novel, photoactivatable method for rapid hepatocyte ablation and ii) developing a deep tissue, 2-photon microscopy live imaging protocol. The molecular factors controlling the identified cell behaviours will be screened for using SILAC-based proteomics. To realise LIVERZAP, expertise in liver research, deep tissue microscopy and proteomics within the host environment will be combined with the fellow’s live imaging experience. LIVERZAP will generate excellent new tools for the regeneration community and greatly enhance the fellow’s competencies in specialised techniques, including cutting-edge microscopy systems and optogenetics. The outcomes of LIVERZAP will produce essential insights into the cellular and molecular mechanisms driving restoration of liver architecture following injury, providing a platform for the long-term development of therapies for human liver pathologies.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания