Nina Graffmann

Projects: LiSyM-Krebs Partnering

Institutions: Universitätsklinikum Düsseldorf - Institut für Stammzellforschung und Regenerative Medizin

https://orcid.org/0000-0002-1229-0792
Nachiket Vartak palproject_administratorasset_housekeeper

Projects: Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), LiSyM network, LiSyM-Krebs Partnering

Institutions: Leibniz-Institut für Arbeitsforschung (IfADo)

https://orcid.org/0000-0001-8813-4799
Johannes Bode

Projects: LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, C-TIP-HCC network

Institutions: Universitätsklinikum Düsseldorf - Klinik für Gastroenterologie, Hepatologie und Infektiologie

Christian Ehlting

Projects: LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network

Institutions: Universitätsklinikum Düsseldorf - Klinik für Gastroenterologie, Hepatologie und Infektiologie

https://orcid.org/0000-0003-0103-1856
SOP : Western diat mouse housing and feeding
Forschungsnetzwerk LiSyM-Krebs, SMART-NAFLD

SOP Western diat mouse housing and feeding

Creator: Ina Biermayer

Submitter: Olga Krebs

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Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.
Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

Abstract (Expand)

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic … development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.

Authors: C. Mayer, S. Nehring, M. Kucken, U. Repnik, S. Seifert, A. Sljukic, J. Delpierre, H. Morales-Navarrete, S. Hinz, M. Brosch, B. Chung, T. Karlsen, M. Huch, Y. Kalaidzidis, L. Brusch, J. Hampe, C. Schafmayer, M. Zerial

Date Published: 31st Jul 2023

Publication Type: Journal

Diploid hepatocytes drive physiological liver renewal in adult humans
DEEP-HCC network

Abstract (Expand)

Physiological liver cell replacement is central to maintaining the organ’s high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (14C) … birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.

Authors: Paula Heinke, Fabian Rost, Julian Rode, Palina Trus, Irina Simonova, Enikő Lázár, Joshua Feddema, Thilo Welsch, Kanar Alkass, Mehran Salehpour, Andrea Zimmermann, Daniel Seehofer, Göran Possnert, Georg Damm, Henrik Druid, Lutz Brusch, Olaf Bergmann

Date Published: 1st Jun 2022

Publication Type: Journal

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