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Javier Bregante*, Flaminia Kaluthantrige Don*, Fabian Rost, André Gohr, German Belenguer, Franziska Baenke, Dylan Liabeuf, Jessie Pöche, Clemens Schafmayer, Michaela Wilsch-Bräuninger, Sebastian Hinz, Kevin O' Holleran, Daniel E Stange, Meritxell Huch
Human liver cholangiocyte organoids capture the heterogeneity of in vivo liver ductal epithelium.
Cell Rep, 45(1) Art. No. 116786 (2026)
Open Access Source   

Human liver ductal epithelium is morphologically, functionally, and transcriptionally heterogeneous. Under- standing the impact of this heterogeneity has been challenging due to the absence of systems that recapit- ulate this heterogeneity in vitro. Here, we found that human liver cholangiocyte organoids do not retain the complex cellular heterogeneity of the native ductal epithelium. Inspired by the knowledge of the cellular niche, we refined our previous organoid medium to fully capture the in vivo cellular heterogeneity. We em- ployed this refined system to analyze the relationships between human biliary epithelial cell states. In our refined model, cholangiocytes transition toward hepatocyte-like states through a bipotent state. Additionally, inhibiting WNT signaling enhances the differentiation capacity of the cells toward hepatocyte-like states. By capturing the in vivo cholangiocyte heterogeneity, our improved organoid model represents a platform to investigate the impact of the different liver ductal cell states in cell plasticity, regeneration, and disease.
@article{Bregante9115,
author={Javier Bregante, Flaminia Kaluthantrige Don, Fabian Rost, André Gohr, German Belenguer, Franziska Baenke, Dylan Liabeuf, Jessie Pöche, Clemens Schafmayer, Michaela Wilsch-Bräuninger, Sebastian Hinz, Kevin O' Holleran, Daniel E Stange, Meritxell Huch},
title={Human liver cholangiocyte organoids capture the heterogeneity of in vivo liver ductal epithelium.},
journal ={Cell reports},
volume={45},
issue ={1},
pages={null--null},
year=2026
}

Madlen Matz-Soja*, Christiane Körner*, Fritzi Ott, Janett Fischer, Eugenia Marbach-Breitrück, Christian Bergmann, Ute Hofmann, Andrej Shevchenko, Iwona Wallach, Kathrin Textoris-Taube, Michael Mülleder, Rolf Gebhardt, Thomas Berg, Nikolaus Berndt
Modeling the dynamics of hepatic metabolism: the predominance of 12-hour rhythmicity in metabolic adaptation.
Cell Mol Life Sci, Art. No. doi: 10.1007/s00018-025-06046-4 (2026)
Open Access PubMed Source   

The liver continuously adjusts its metabolic activity to synchronize the nutrient supply with the body's demands. This synchronization involves the complex coordination of acute metabolic needs, nutrient availability, and activity levels, which is orchestrated according to cyclic internal rhythms governed by the circadian clock. This study aimed to decipher the role of circadian rhythms in liver metabolic functions, including mitochondrial activities that are critical for energy production and metabolic adaptation.
@article{Matz-Soja9122,
author={Madlen Matz-Soja, Christiane Körner, Fritzi Ott, Janett Fischer, Eugenia Marbach-Breitrück, Christian Bergmann, Ute Hofmann, Andrej Shevchenko, Iwona Wallach, Kathrin Textoris-Taube, Michael Mülleder, Rolf Gebhardt, Thomas Berg, Nikolaus Berndt},
title={Modeling the dynamics of hepatic metabolism: the predominance of 12-hour rhythmicity in metabolic adaptation.},
journal ={Cellular and molecular life sciences : CMLS},
volume={},
pages={1--1},
year=2026
}

Alison Kickuth, Urša Uršič, Michael F Staddon, Jan Brugués
A mechanical ratchet drives unilateral cytokinesis.
Nature, Art. No. doi: 10.1038/s41586-025-09915-x (2026)
Open Access PubMed Source   

The canonical mechanism that drives cell division comprises the formation and constriction of a contractile actin ring1-3. However, this mechanism is not compatible with the early development of many vertebrates4-9. Yolk-anchored embryos typically cannot form a complete ring during early cleavage divisions, but it remains unclear how a partial circular arc with loose ends can divide the cell. Here, by combining laser ablation of the cytokinetic band with rheological measurements in vivo, we show that stiffening of the bulk cytoplasm, mediated by the interphase microtubule network, stabilizes the contractile band by anchoring it along its length during growth. Conversely, as the cell cycle progresses, the cytoplasm fluidizes, diminishing band-cytoplasmic anchoring and facilitating band ingression. This dynamic interplay between stability and growth versus instability and ingression repeats for several cell cycles until division is complete, resulting in a mechanical ratchet that drives cell division. Our study underscores the role of temporal control over cytoplasmic rheology as a key feature that drives unilateral cytokinesis in the absence of a closed actin ring.
@article{Kickuth9124,
author={Alison Kickuth, Urša Uršič, Michael F Staddon, Jan Brugués},
title={A mechanical ratchet drives unilateral cytokinesis.},
journal ={Nature},
volume={},
pages={1--1},
year=2026
}

Jinjin Zhang, Xiuping Zhang, Ningyawen Liu, Jiang Hu, Michael Hiller, Virag Sharma, Fengming Han, He Dai, Xiaolong Tu, David N Cooper, Dong-Dong Wu, Lin Zeng
A POMT2 missense substitution contributes to hypoxia adaptation in hibernating mammals.
Mol Biol Evol, Art. No. doi: 10.1093/molbev/msag001 (2026)
PubMed Source   

Hibernation is an adaptive survival strategy used by animals to cope with extreme environmental conditions. Although this physiological process involves complex metabolic changes, its underlying biological mechanisms remain largely unknown. Through comparative genomic analysis of six hibernating species across five orders, we identified an ancient amino acid substitution in POMT2 (R708Q), exhibiting signals of both convergent and positive selection in hibernating mammals. Phylogenetic analysis using HeIST indicated hemiplasy as a possible explanation, though given mammalian divergence times and the broader evidence for convergence, this is best considered an alternative rather than the primary interpretation. Functional studies using transgenic mice demonstrated the contribution of this mutation to hypoxia adaptation. Notably, despite the absence of this mutation in Rodentia hibernators, we included Graphiurus kelleni as a positive control in physiological studies of transgenic mice carrying POMT2(R708Q), given its remarkable hypoxia adaptation during hibernation. Our findings not only provide novel insights into the genetic basis of hypoxic adaptation in hibernating mammals but also suggest incomplete lineage sorting (hemiplasy) as a plausible evolutionary mechanism for this important adaptive trait.
@article{Zhang9125,
author={Jinjin Zhang, Xiuping Zhang, Ningyawen Liu, Jiang Hu, Michael Hiller, Virag Sharma, Fengming Han, He Dai, Xiaolong Tu, David N Cooper, Dong-Dong Wu, Lin Zeng},
title={A POMT2 missense substitution contributes to hypoxia adaptation in hibernating mammals.},
journal ={Molecular biology and evolution},
volume={},
pages={1--1},
year=2026
}

Anna Hadarovich, Maxim Scheremetjew, Hari Raj Singh, HongKee Moon, Lena Hersemann, Agnes Toth-Petroczy
PICNIC web server for predicting proteins involved in biomolecular condensates.
Bioinformatics, 42(1) Art. No. btaf647 (2026)
Open Access PubMed Source   

Biomolecular condensates have been implicated in key cellular processes such as gene regulation, stress response, and signaling, and dysregulation of condensates has been linked to neurodegeneration and other diseases. Computational algorithms that predict protein condensation can aid systematic characterization of biomolecular condensates at the proteome scale. However, many experimental labs may lack the computational background or resources to run sophisticated prediction tools locally.
@article{Hadarovich9095,
author={Anna Hadarovich, Maxim Scheremetjew, Hari Raj Singh, HongKee Moon, Lena Hersemann, Agnes Toth-Petroczy},
title={PICNIC web server for predicting proteins involved in biomolecular condensates.},
journal ={Bioinformatics (Oxford, England)},
volume={42},
issue ={1},
pages={1--1},
year=2026
}

Samrat Basak*, Kim-Chi Vu*, Nikolaos Mougios*, Nazar Oleksiievets, Yoav G Pollack, Sören Brandenburg, Felipe Opazo, Stephan E Lehnart, Jörg Enderlein#, Roman Tsukanov#
Versatile Microfluidics Platform for Enhanced Multitarget Super-Resolution Microscopy.
ACS Nano, Art. No. doi: 10.1021/acsnano.5c18697 (2026)
Open Access PubMed Source   

DNA-based Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) is a powerful variant of single-molecule localization microscopy (SMLM) that overcomes the limitations of photobleaching, offers flexible fluorophore selection, and enables fine control of imaging parameters through tunable on- and off-binding kinetics. Its most distinctive feature is its capacity for multiplexing, typically implemented through sequential imaging of targets using an Exchange-PAINT. This technique involves assigning orthogonal DNA strands to different targets within a sample and then sequentially adding and removing complementary imager strands that are specific to only one target at a time. However, manual Exchange-PAINT workflows are often inefficient, prone to drift and variability, and lack reproducibility. Here, we introduce a custom compressed-air-driven microfluidics system specifically designed for multiplexed SMLM. Featuring a stackable and modular design that is, in principle, not limited by the number of channels, the system ensures robust, reproducible, and material-efficient buffer exchange with minimal dead volume. It operates in both manual and automated modes and can be readily adapted to a wide range of commercial and custom microscopes, including wide-field, confocal, STED, MINFLUX and other platforms. We demonstrate robust 5-plex Exchange-PAINT imaging in cancerous U2OS cells, and importantly, we establish multiplexed nanoscale imaging in fragile primary cardiomyocytes. These applications demonstrate that the platform enables reliable super-resolution multiplexing in physiologically relevant systems and supports detailed nanoscale analysis in complex primary cells.
@article{Basak9109,
author={Samrat Basak, Kim-Chi Vu, Nikolaos Mougios, Nazar Oleksiievets, Yoav G Pollack, Sören Brandenburg, Felipe Opazo, Stephan E Lehnart, Jörg Enderlein, Roman Tsukanov},
title={Versatile Microfluidics Platform for Enhanced Multitarget Super-Resolution Microscopy.},
journal ={ACS nano},
volume={},
pages={1--1},
year=2026
}

Olivier N Lemaire*#, Mélissa Belhamri*, Anna Shevchenko, Tristan Wagner#
Carbon-monoxide-driven bioethanol production operates through a tungsten-dependent catalyst.
Nat Chem Biol, 22(1) 28-36 (2026)
Open Access PubMed Source   

Microbial alcohol production from waste gases is a game changer for sustainable carbon cycling and remediation. While the biotechnological process using Clostridium autoethanogenum to transform syngas (H2, CO2 and CO) is blooming, scientific debates remain on the ethanol biosynthesis pathway. Here, we experimentally validated that ethanol production is initiated through a tungsten-dependent aldehyde:ferredoxin oxidoreductase (AFOR), which reduces acetate to acetaldehyde. The reaction, thermodynamically unfavorable under standard conditions, has been considered by many as unsuitable in vivo but is rather approved by metabolic modeling. To answer this riddle, we demonstrated that the thermodynamic coupling of CO oxidation and ethanol synthesis allows acetate reduction. The experiments, performed with native CO dehydrogenase and AFOR, highlighted the key role of ferredoxin in stimulating the activity of both metalloenzymes and electron shuttling. The crystal structure of holo AFOR, refined to 1.59-Å resolution, and its biochemical characterization provide new insights into the cofactor chemistry and the specificities of this enzyme, fundamental to sustainable biofuel production.
@article{Lemaire9080,
author={Olivier N Lemaire, Mélissa Belhamri, Anna Shevchenko, Tristan Wagner},
title={Carbon-monoxide-driven bioethanol production operates through a tungsten-dependent catalyst.},
journal ={Nature chemical biology},
volume={22},
issue ={1},
pages={28--36},
year=2026
}

Aleksandra Sljukic*, Joshua Green Jenkinson*, Armin Niksic*, Nicole Prior#, Meritxell Huch#
Advances in liver and pancreas organoids: how far we have come and where we go next.
Nat Rev Gastroenterol Hepatol, 23(1) 44-64 (2026)
Open Access PubMed Source   

Over the past decade, advances in organoid culturing methods have enabled the growth of three-dimensional cellular cultures in vitro with increasing fidelity with respect to the cellular composition, architecture and function of in vivo organs. The increased accessibility and ability to manipulate organoids as an in vitro system have led to a shift in the landscape of experimental biology. Whether derived from stem cells or tissue-resident cells, organoids are now routinely used in studies of development, homeostasis, regeneration and disease modelling, including viral infection and cancer. These applications of organoids are highly relevant for gastrointestinal tissues, including the liver and pancreas. In this Review, we explore the current and emerging advances in liver and pancreas organoid technologies for both discovery and clinical translation research and provide an outlook on the challenges ahead.
@article{Sljukic9068,
author={Aleksandra Sljukic, Joshua Green Jenkinson, Armin Niksic, Nicole Prior, Meritxell Huch},
title={Advances in liver and pancreas organoids: how far we have come and where we go next.},
journal ={Nature reviews. Gastroenterology & hepatology},
volume={23},
issue ={1},
pages={44--64},
year=2026
}

Reemon Spector, Heather A Harrington, Eamonn A Gaffney
Persistent Homology Classifies Parameter Dependence of Patterns in Turing Systems.
Bull Math Biol, 88(1) Art. No. 10 (2026)
Open Access PubMed Source   

This paper illustrates a further application of topological data analysis to the study of self-organising models for chemical and biological systems. In particular, we investigate whether topological summaries can capture the parameter dependence of pattern topology in reaction diffusion systems, by examining the homology of sublevel sets of solutions to Turing reaction diffusion systems for a range of parameters. We demonstrate that a topological clustering algorithm can reveal how pattern topology depends on parameters, using the chlorite-iodide-malonic acid system, and the prototypical Schnakenberg system for illustration. In addition, we discuss the prospective application of such clustering, for instance in refining priors for detailed parameter estimation for self-organising systems.
@article{Spector9105,
author={Reemon Spector, Heather A Harrington, Eamonn A Gaffney},
title={Persistent Homology Classifies Parameter Dependence of Patterns in Turing Systems.},
journal ={Bulletin of mathematical biology},
volume={88},
issue ={1},
pages={null--null},
year=2026
}

Julian Kompa, Lars J Dornfeld, Nicola Porzberg, SoRi Jang, Silja Zedlitz, Simon H Lilje, Claudia Catapano, David Jocher, Lukas Merk, Carsten Hoege, Runyu Mao, Jonas Wilhelm, Marina S Dietz, Miroslaw Tarnawski, Julien Hiblot, Anthony Hyman, Mike Heilemann, Kai Johnsson
Fast, Bright, and Reversible Fluorescent Labeling of Rhodamine-Binding Proteins.
J Am Chem Soc, Art. No. doi: 10.1021/jacs.5c18083 (2025)
Open Access PubMed Source   

Rhodamine dyes conjugated to targeting ligands can yield exceptionally bright fluorescent probes for live-cell imaging. However, the limited permeability of such rhodamine derivatives restricts their broader applications, particularly in vivo. Here, we present Rho-tag and SiR-tag, engineered protein tags derived from bacterial multidrug-resistant proteins that bind unsubstituted (silicon) rhodamines with nanomolar affinity. Unsubstituted (silicon) rhodamines readily cross membranes and enable rapid, reversible, and fluorogenic labeling of the tags in mammalian cells within seconds. The labeling of Rho-tag and SiR-tag is compatible with various super-resolution imaging methods and allows their use alongside self-labeling tags, such as HaloTag7 and SNAP-tag. The high affinity and specificity of both tags, combined with the permeability and outstanding spectroscopic properties of rhodamines, make them particularly attractive for in vivo bioimaging, as demonstrated by efficient fluorescent labeling inC. elegansembryos and zebrafish larvae.
@article{Kompa9110,
author={Julian Kompa, Lars J Dornfeld, Nicola Porzberg, SoRi Jang, Silja Zedlitz, Simon H Lilje, Claudia Catapano, David Jocher, Lukas Merk, Carsten Hoege, Runyu Mao, Jonas Wilhelm, Marina S Dietz, Miroslaw Tarnawski, Julien Hiblot, Anthony Hyman, Mike Heilemann, Kai Johnsson},
title={Fast, Bright, and Reversible Fluorescent Labeling of Rhodamine-Binding Proteins.},
journal ={Journal of the American Chemical Society},
volume={},
pages={1--1},
year=2025
}


* joint first authors, # joint corresponding authors