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7 results on '"Jenny Hetzer"'

1. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Author

Emilie Crouchet, Simonetta Bandiera, Naoto Fujiwara, Shen Li, Hussein El Saghire, Mirian Fernández-Vaquero, Tobias Riedl, Xiaochen Sun, Hadassa Hirschfield, Frank Jühling, Shijia Zhu, Natascha Roehlen, Clara Ponsolles, Laura Heydmann, Antonio Saviano, Tongqi Qian, Anu Venkatesh, Joachim Lupberger, Eloi R. Verrier, Mozhdeh Sojoodi, Marine A. Oudot, François H. T. Duong, Ricard Masia, Lan Wei, Christine Thumann, Sarah C. Durand, Victor González-Motos, Danijela Heide, Jenny Hetzer, Shigeki Nakagawa, Atsushi Ono, Won-Min Song, Takaaki Higashi, Roberto Sanchez, Rosa S. Kim, C. Billie Bian, Karun Kiani, Tom Croonenborghs, Aravind Subramanian, Raymond T. Chung, Beate K. Straub, Detlef Schuppan, Maliki Ankavay, Laurence Cocquerel, Evelyne Schaeffer, Nicolas Goossens, Anna P. Koh, Milind Mahajan, Venugopalan D. Nair, Ganesh Gunasekaran, Myron E. Schwartz, Nabeel Bardeesy, Alex K. Shalek, Orit Rozenblatt-Rosen, Aviv Regev, Emanuele Felli, Patrick Pessaux, Kenneth K. Tanabe, Mathias Heikenwälder, Catherine Schuster, Nathalie Pochet, Mirjam B. Zeisel, Bryan C. Fuchs, Yujin Hoshida, and Thomas F. Baumert

Subjects
Science
Abstract

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

Published
2021
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2. Epithelial cells of the intestine acquire cell-intrinsic inflammation signatures during ageing

Author

Maja C. Funk, Jan G. Gleixner, Florian Heigwer, Erica Valentini, Zeynep Aydin, Elena Tonin, Jenny Hetzer, Danijela Heide, Oliver Stegle, Mathias Heikenwalder, and Michael Boutros

Abstract

During ageing, cell-intrinsic and extrinsic factors lead to the decline of tissue function and organismal health. Disentangling these factors is important for developing effective strategies to prolong organismal healthspan. Here, we addressed this question in the mouse intestinal epithelium, which forms a dynamic interface with its microenvironment and receives extrinsic signals affecting its homeostasis and tissue ageing. We systematically compared transcriptional profiles of young and aged epithelial cells in vivo and ex vivo in cultured intestinal organoids. We found that all cell types of the aged epithelium exhibit an inflammation phenotype, which is marked by MHC class II upregulation and most pronounced in enterocytes. This was accompanied by elevated levels of the immune tolerance markers PD-1 and PD-L1 in the aged tissue microenvironment, indicating dysregulation of immunological homeostasis. Intestinal organoids from aged mice still showed an inflammation signature after weeks in culture, which was concurrent with increased chromatin accessibility of inflammation-associated loci. Our results reveal a cell-intrinsic, persistent inflammation phenotype in aged epithelial cells, which might contribute to systemic inflammation observed during ageing.

Published
2021
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3. Peroxiredoxin 2 is a target for hepatocellular carcinoma chemoprevention

Author

Emilie Crouchet, Eugénie Schaeffer, Hussein El Saghire, Naoto Fujiwara, Frank Jühling, Marine Oudot, Clara Ponsolles, Nicolas Brignon, Sarah Durand, Marie Parnot, Danijela Heide, Jenny Hetzer, Mathias Heikenwälder, Emanuele Felli, Patrick Pessaux, Nathalie Pochet, Yujin Hoshida, Laurent Mailly, Thomas Baumert, and Catherine Schuster

Subjects
Hepatology
Published
2022
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4. A human liver cell-based system modeling a clinical prognostic liver signature combined with single cell RNA-seq for discovery of novel liver disease therapeutics

Author

Emilie Crouchet, Simonetta Bandiera, Naoto Fujiwara, Shen Li, Hussein El Saghire, Xiaochen Sun, Hadassa Hirschfield, Natascha Roehlen, Frank Jühling, Antonio Saviano, Victor Gonzalez-Motos, Anu Venkatesh, Clara Ponsolles, Eloi Verrier, Nicolaas Van Renne, Joachim Lupberger, Christine Thumann, François H.T. Duong, Shijia Zhu, Mozhdeh Sojoodi, Ricard Masia, Lan Wei, Marine Oudot, Sarah Durand, Shigeki Nakagawa, Atsushi Ono, Won-Min Song, Takaaki Higashi, Roberto Sanchez, Rosa S. Kim, C. Billie Bian, Karun Kiani, Tom Croonenborghs, Aravind Subramanian, Raymond Chung, Danijela Heide, Jenny Hetzer, Beate Straub, Detlef Schuppan, Maliki Ankavay, Laurence Cocquerel, Evelyne Schaeffer, Nicolas Goossens, Anna P. Koh, Milind Mahajan, Venugopalan D. Nair, Ganesh Gunasekaran, Myron Schwartz, Nabeel Bardeesy, Alex K. Shalek, Orit Rozenblatt-Rosen, Aviv Regev, Mathias Heikenwalder, Emanuele Felli, Patrick Pessaux, Kenneth K. Tanabe, Catherine Schuster, Nathalie Pochet, Mirjam Zeisel, Bryan C. Fuchs, Yujin Hoshida, and Thomas Baumert

Subjects
Hepatology
Published
2020
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5. Inhibition of LTβR signalling activates WNT-induced regeneration in lung

Author

Zeynep Ertüz, Giorgi Beroshvili, Dominik Pfister, Adrien Guillot, Oliver Eickelberg, Mathias Heikenwalder, Eric Goffin, Reinoud Gosens, Gerald Burgstaller, Danijela Heide, Maximilian Strunz, Fabian J. Theis, Mareike Lehmann, Martin A. Lopez, Michael Boutros, Aicha Jeridi, Darcy E. Wagner, Yan Hu, Marlene Kohlhepp, Tracy O'Connor, Lore Becker, Frank Tacke, Thomas M. Conlon, Meshal Ansari, Indrabahadur Singh, Christoph Mayr, Martin Hrabé de Angelis, Tobias Stoeger, Emmanuel Dejardin, Hani N. Alsafadi, Melanie Königshoff, Sandra Prokosch, Chiara Ciminieri, Michael Dudek, Bernard Pirotte, Herbert B. Schiller, Johannes Beckers, Maja C. Funk, Percy A. Knolle, Martin Irmler, Stijn E. Verleden, Michael Lindner, Gizem Gunes, Rita Costa, Jenny Hetzer, Gerrit John-Schuster, Jakob Janzen, Ali Önder Yildirim, Groningen Research Institute for Asthma and COPD (GRIAC), Molecular Pharmacology, and Nanomedicine & Drug Targeting

Subjects
0301 basic medicine, Aging, Apoptosis, Adaptive Immunity, Article, 03 medical and health sciences, Mice, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Fibrosis, Lymphotoxin beta Receptor, Smoke, medicine, Animals, Humans, Regeneration, Progenitor cell, Lung, beta Catenin, Emphysema, Multidisciplinary, Innate immune system, business.industry, Regeneration (biology), Stem Cells, Wnt signaling pathway, NF-kappa B, Acquired immune system, medicine.disease, Epithelium, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Wnt Proteins, 030104 developmental biology, Lymphotoxin, medicine.anatomical_structure, 030228 respiratory system, Alveolar Epithelial Cells, Cancer research, Female, business, Engineering sciences. Technology, Signal Transduction
Abstract

Blockade of lymphotoxin beta-receptor (LT beta R) signalling restores WNT signalling and epithelial repair in a model of chronic obstructive pulmonary disease. Lymphotoxin beta-receptor (LT beta R) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures(1,2), which are associated with severe chronic inflammatory diseases that span several organ systems(3-6). How LT beta R signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LT beta R blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LT beta R ligands in adaptive and innate immune cells, enhanced non-canonical NF-kappa B signalling, and enriched LT beta R target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LT beta R signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LT beta R signalling dampened epithelial non-canonical activation of NF-kappa B, reduced TGF beta signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/beta-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LT beta R signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures(1) and inhibition of apoptosis with tissue-regenerative strategies.

Published
2019

6. Publisher Correction: Inhibition of LTβR signalling activates WNT-induced regeneration in lung

Author

Dominik Pfister, Adrien Guillot, Frank Tacke, Zeynep Ertüz, Thomas M. Conlon, Meshal Ansari, Gizem Gunes, Indrabahadur Singh, Ilias Angelidis, Maja C. Funk, Darcy E. Wagner, Gerrit John-Schuster, Emmanuel Dejardin, Michael Lindner, Mareike Lehmann, Jenny Hetzer, Bernard Pirotte, Jakob Janzen, Martin Irmler, Tracy O'Connor, Lore Becker, Mathias Heikenwalder, Giorgi Beroshvili, Yan Hu, Michael Boutros, Johannes Beckers, Ali Önder Yildirim, Reinoud Gosens, Fabian J. Theis, Danijela Heide, Maximilian Strunz, Stijn E. Verleden, Melanie Königshoff, Martin Hrabé de Angelis, Gerald Burgstaller, Eric Goffin, Tobias Stoeger, Martin A. Lopez, Hani N. Alsafadi, Aicha Jeridi, Marlene Kohlhepp, Chiara Ciminieri, Percy A. Knolle, Christoph Mayr, Oliver Eickelberg, Michael Dudek, Sandra Prokosch, Herbert B. Schiller, and Rita Costa

Subjects
Cellular immunity, Multidisciplinary, Signalling, Lung, medicine.anatomical_structure, business.industry, Regeneration (biology), medicine, Wnt signaling pathway, business, Cell biology
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03087-6

Published
2021
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7. Single cell RNA-seq of patient liver tissues uncover HRH2+/CLEC5a high/macro low macrophages as therapeutic target for the treatment of liver fibrosis and cancer prevention

Author

Emilie Crouchet, Simonetta Bandiera, Naoto Fujiwara, Shen Li, Hussein El Saghire, Xiaochen Sun, Hadassa Hirschfield, Natascha Roehlen, Frank Jühling, Antonio Saviano, Victor Gonzalez-Motos, Anu Venkatesh, Clara Ponsolles, Joachim Lupberger, François H.T. Duong, Shijia Zhu, Mozhdeh Sojoodi, Ricard Masia, Lan Wei, Marine Oudot, Sarah Durand, Shigeki Nakagawa, Atsushi Ono, Won-Min Song, Takaaki Higashi, Rosa S. Kim, C Billie Bian, Tom Croonenborghs, Raymond Chung, Danijela Heide, Jenny Hetzer, Beate Straub, Detlef Schuppan, Anna P. Koh, Milind Mahajan, Mathias Heikenwalder, Emanuele Felli, Patrick Pessaux, Kenneth K. Tanabe, Catherine Schuster, Nathalie Pochet, Mirjam Zeisel, Bryan C. Fuchs, Yujin Hoshida, and Thomas Baumert

Subjects
Hepatology
Published
2020
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