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Jessica Thiel, Duran Sürün, Desiree C Brändle, Madeleine Teichert, Stephan R Künzel, Ulrike Friedrich, Andreas Dahl, Kristin Schubert, Ignacy Rzagalinski, Andrej Shevchenko, Sofia Traikov, Peter Mirtschink, Lisa Wagenführ, Frank Buchholz, Kristina Hölig, Torsten Tonn, Romy Kronstein-Wiedemann
Knock Out of miRNA-30a-5p and Reconstitution of the Actin Network Dynamics Partly Restores the Impaired Terminal Erythroid Differentiation during Blood Pharming.
Stem Cell Rev Rep, 21(8) 2637-2653 (2025)
Open Access PubMed Source   

In vitro red blood cell (RBC) production offers a promising complement to conventional blood donation, particularly for patients with rare blood types. Previously, we developed imBMEP-A, the first erythroid cell line derived from reticulocyte progenitors, which maintains robust hemoglobin expression and erythroid differentiation in the presence of erythropoietin (EPO) despite its immortalized state. However, clinical translation remains hindered by the inability to scale up production due to impaired in vitro enucleation of RBC progenitor cell lines. Enhancing enucleation efficiency in imBMEP-A cells involved CRISPR/Cas9-mediated knockout (K.O.) of miR-30a-5p, a key enucleation inhibitor, moderately increasing rates to 3.3 ± 0.4%- 8.9 ± 1.7%. Further investigation of enucleation inefficiencies led to transcriptome and proteome comparisons between imBMEP-miR30a-K.O. cells and hematopoietic stem cells (HSCs). These analyses revealed altered gene expression and protein abundances linked to metabolic transitions, apoptosis promotion, and cytoskeletal regulation. Notably, forced expression of the proto-oncogene c-Myc, required for cell immortalization, emerged as a key driver of these physiological changes. Counteracting these effects required optimization of imBMEP-A cells by activating BCL-XL transcription and knocking out SCIN, which encodes the actin-severing protein scinderin. While BCL-XL is upregulated in normal erythropoiesis, it is downregulated in imBMEP-A. Conversely, SCIN, typically absent in erythroid cells, is highly expressed in imBMEP-A, disrupting actin organization. These interventions improved viability, restored actin network formation, and increased terminal erythropoiesis, yielding 22.1 ± 1.7% more orthochromatic erythroblasts. These findings establish a foundation for optimizing imBMEP-A cells for therapeutic use and advancing the understanding the pathophysiology of erythroleukemia.
@article{Thiel9053,
author={Jessica Thiel, Duran Sürün, Desiree C Brändle, Madeleine Teichert, Stephan R Künzel, Ulrike Friedrich, Andreas Dahl, Kristin Schubert, Ignacy Rzagalinski, Andrej Shevchenko, Sofia Traikov, Peter Mirtschink, Lisa Wagenführ, Frank Buchholz, Kristina Hölig, Torsten Tonn, Romy Kronstein-Wiedemann},
title={Knock Out of miRNA-30a-5p and Reconstitution of the Actin Network Dynamics Partly Restores the Impaired Terminal Erythroid Differentiation during Blood Pharming.},
journal ={Stem cell reviews and reports},
volume={21},
issue ={8},
pages={2637--2653},
year=2025
}

Xinyi Yang, Teresa Ferraro, Kelly Molnar, Julien Pontabry, Sam-Rayden Malanda, Nicola Maghelli, Loic Royer, Stephan W. Grill, Gene Myers, Silvia Grigolon, Michel Labouesse
Repeated extrinsic and anisotropic mechanical inputs promote C. elegans polarized adherens junction elongation.
Dev Cell, 60(20) 2777-2790 (2025)
Open Access PubMed Source   

A key challenge in development is understanding how complex organisms physically coordinate the morphogenesis of multiple tissues. Here, using biophysical approaches, we investigate how muscles under the epidermis specifically stimulate the extension of anterior-posterior (AP)-oriented epidermal adherens junctions during late C. elegans embryonic elongation. First, light-sheet imaging shows that asynchronous patterns of muscle contractions drive embryo rotations. In turn, junctions between the lateral and dorso-ventral epidermis repeatedly oscillate between a folded, hypotensed state and an extended, hypertensed state. Second, fluorescence recovery after photobleaching (FRAP) analysis of an E-cadherin::GFP construct shows that muscle contractions stimulate E-cadherin turnover. Moreover, a mechano-chemical model backed by genetic tests suggests that E-cadherin trafficking controls junction elongation due to lower line tension. Altogether, our results illustrate how muscle contractions fluidize epidermal adherens junctions, which, combined with anisotropic tension in the epidermis, drive their polarized extension.
@article{Yang9021,
author={Xinyi Yang, Teresa Ferraro, Kelly Molnar, Julien Pontabry, Sam-Rayden Malanda, Nicola Maghelli, Loic Royer, Stephan W. Grill, Gene Myers, Silvia Grigolon, Michel Labouesse},
title={Repeated extrinsic and anisotropic mechanical inputs promote C. elegans polarized adherens junction elongation.},
journal ={Developmental cell},
volume={60},
issue ={20},
pages={2777--2790},
year=2025
}

Meritxell Huch, Saanjbati Adhikari
An interview with Meritxell (Meri) Huch.
Development, 152(20) Art. No. dev205227 (2025)
PubMed Source   

Meritxell (Meri) Huch is a Director and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, where her group uses 3D organoid models to study the maintenance and repair of adult tissues, as well as the mechanisms by which their dysregulation contributes to disease. This year, Meri is a Guest Editor for Development's special issue on lifelong development, which highlights how developmental processes and pathways are used throughout animal lifespans. We caught up with Meri over Teams to discuss the importance of using organoid models to study tissue regeneration and pathology, as well as some of the most exciting research questions that her lab is trying to answer.
@article{Huch9072,
author={Meritxell Huch, Saanjbati Adhikari},
title={An interview with Meritxell (Meri) Huch.},
journal ={Development (Cambridge, England)},
volume={152},
issue ={20},
pages={null--null},
year=2025
}

Maria Torras-Pérez, Iris H R Yoon, Praveen Weeratunga, Ling-Pei Ho, Helen M Byrne, Ulrike Tillmann, Heather A Harrington
Topology across scales on heterogeneous cell data.
PLoS Comput Biol, 21(10) Art. No. e1013460 (2025)
Open Access PubMed Source   

Multiplexed imaging allows multiple cell types to be simultaneously visualised in a single tissue sample, generating unprecedented amounts of spatially-resolved, biological data. In topological data analysis, persistent homology provides multiscale descriptors of "shape" suitable for the analysis of such spatial data. Here we propose a novel visualisation of persistent homology (PH) and fine-tune vectorisations thereof (exploring the effect of different weightings for persistence images, a prominent vectorisation of PH). These approaches offer new biological interpretations and promising avenues for improving the analysis of complex spatial biological data especially in multiple cell type data. To illustrate our methods, we apply them to a lung data set from fatal cases of COVID-19 and a data set from lupus murine spleen.
@article{Torras-Pérez9071,
author={Maria Torras-Pérez, Iris H R Yoon, Praveen Weeratunga, Ling-Pei Ho, Helen M Byrne, Ulrike Tillmann, Heather A Harrington},
title={Topology across scales on heterogeneous cell data.},
journal ={PLoS computational biology},
volume={21},
issue ={10},
pages={null--null},
year=2025
}

Carlotta Mayer
The Role of Bile Pressure in Bile Canaliculi Remodeling and Liver Disease.
Ph.D. Thesis, Technische Universität Dresden, Dresden, Germany (2025)
 

@phdthesis{Mayer9076,
author = {Carlotta Mayer},
title={The Role of Bile Pressure in Bile Canaliculi Remodeling and Liver Disease.},
school = {Technische Universität Dresden},
year=2025,
address = {Dresden, Germany},
}

Sophie Achilles, Jan-Niklas Tomczak, Fabiane-Samira Baumann, Bassam G Haddad, Stefan Oswald, Jan-Philipp Machtens, Eric R Geertsma, Ilka Wittig, Georg Lamprecht
N-glycans on SLC26A3 do not significantly alter plasma membrane or lipid raft trafficking, but appear to stabilize interdomain contacts to stimulate transport.
Am J Physiol Gastrointest Liver Physiol, Art. No. doi: 10.1152/ajpgi.00362.2024 (2025)
Open Access PubMed Source   

DRA (SLC26A3) is a major apical intestinal Cl-/HCO3- exchanger, which is expressed in complex and hybrid N-glycosylated forms. While the importance of N-glycosylation is evident from the significantly reduced transport activity of non-N-glycosylated DRA constructs (DRA-N0), the underlying molecular mechanisms are controversial. Therefore, plasma membrane expression and lipid raft localization of glycosylation-deficient DRA-N0 were analyzed in HEK cells. The activity of DRA-N0 was reduced by 70% compared to the wildtype construct. Absolute expression of DRA-N0 was significantly reduced by approximately 57% in the cell lysate and by 34 and 45% in the plasma membrane and in plasma membrane-derived lipid rafts, respectively. These amounts are insufficient to account for the reduction in activity. Furthermore, the statistical analysis did not support a difference in the relative expression of DRA and DRA-N0 in the plasma membrane and in plasma membrane-derived lipid rafts, indicating that N-glycosylation does not affect transport activity through trafficking and localization in these cell compartments. To gain insight into potential intramolecular effects of N-glycosylation on DRA, its 3D-structure was predicted using AlphaFold3 with complex N-glycans covalently attached to N153, N161, and N164 in the transport domain. This revealed multiple inward- and outward-facing conformations of the protein. The number of interdomain contacts of the transport domain-bound glycans with the scaffold domain was higher in the inward-facing state. Because substrate release to the cytoplasm represents the rate-limiting step in many transport proteins, this suggests that in DRA glycans stabilize the inward-facing state facilitating anion transport.
@article{Achilles9069,
author={Sophie Achilles, Jan-Niklas Tomczak, Fabiane-Samira Baumann, Bassam G Haddad, Stefan Oswald, Jan-Philipp Machtens, Eric R Geertsma, Ilka Wittig, Georg Lamprecht},
title={N-glycans on SLC26A3 do not significantly alter plasma membrane or lipid raft trafficking, but appear to stabilize interdomain contacts to stimulate transport.},
journal ={American journal of physiology. Gastrointestinal and liver physiology},
volume={},
pages={1--1},
year=2025
}

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, Art. No. doi: doi: 10.1038/s41575-025-01116-1 (2025)
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={},
pages={1--1},
year=2025
}

Vincenzo Galgano
Identifiability and singular locus of secant varieties to Spinor varieties.
COMMUNICATIONS IN CONTEMPORARY MATHEMATICS, Art. No. doi: 10.1142/S0219199725500890 (2025)
Source   

In this work, we analyze the Spin-structure of the secant variety of lines sigma(2)(S) to a Spinor variety S minimally embedded in its spin representation. In particular, we determine the poset of the Spin-orbits and their dimensions. We use it for solving the problems of identifiability and tangential-identifiability in sigma(2)(S), and for determining the second Terracini locus of S. Finally, we show that the singular locus Sing(sigma(2)(S)) contains the two Spin-orbits of lowest dimensions and it lies in the tangential variety tau(S): we also conjecture what it set-theoretically is.
@article{Galgano9078,
author={Vincenzo Galgano},
title={Identifiability and singular locus of secant varieties to Spinor varieties.},
journal ={COMMUNICATIONS IN CONTEMPORARY MATHEMATICS},
volume={},
pages={1--1},
year=2025
}

Basusree Ghosh*, Patrick M McCall*, Kristian Le Vay, Archishman Ghosh, Lars Hubatsch, David Thomas Gonzales, Jan Brugués, Hannes Mutschler#, T-Y Dora Tang#
RNA-peptide interactions tune the ribozyme activity within coacervate microdroplet dispersions.
Nat Commun, 16(1) Art. No. 8765 (2025)
Open Access PubMed Source Full Text   

Membrane-free complex coacervate microdroplets are compelling models for primitive compartmentalisation with the ability to form from biological molecules. However, understanding how molecular interactions can influence physicochemical properties and catalytic activity of membrane-free compartments is still in its infancy. This is important for defining the function of membrane-free compartments during the origin of life as well as in modern biology. Here, we use RNA-peptide coacervate microdroplets prepared with prebiotically relevant amino acids and a minimal hammerhead ribozyme. This is a model system to probe the relationship between coacervate composition, its properties and ribozyme activity. We show that ribozyme catalytic activity is inhibited within the coacervate compared to buffer solution, whilst variations in peptide sequence can modulate rates and yield of the ribozyme within the coacervate droplet by up to 15-fold. The apparent ribozyme rate constant is anti-correlated with its concentration and correlated to its diffusion coefficient within the coacervates. Our results provide a relationship between the physicochemical properties of the coacervate microenvironment and the catalytic activity of the ribozyme where membrane-free compartments could provide a selection pressure to drive molecular evolution on prebiotic earth.
@article{Ghosh9066,
author={Basusree Ghosh, Patrick M McCall, Kristian Le Vay, Archishman Ghosh, Lars Hubatsch, David Thomas Gonzales, Jan Brugués, Hannes Mutschler, T-Y Dora Tang},
title={RNA-peptide interactions tune the ribozyme activity within coacervate microdroplet dispersions.},
journal ={Nature communications},
volume={16},
issue ={1},
pages={null--null},
year=2025
}

Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy
On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.
Annu Rev Cell Dev Biol, 41(1) 403-432 (2025)
Open Access PubMed Source   

Biomolecular condensates provide a way to compartmentalize subcellular components with high temporal and spatial resolution, enabling rapid responses to signals and environmental changes. While the formation, components, and function of some condensates are well-characterized, their presence across organisms, their evolutionary history, and their origin are less well-understood. Here, we review the diversity of condensate components and highlight that not only disordered but also fully structured proteins are capable of driving condensate formation. We compare how proteomes of condensates overlap within and across species, and we present functionally analogous condensates across organisms. Additionally, we discuss the potential role of condensation in early life, suggesting that phase separation could have facilitated the selection and concentration of prebiotic molecules, promoting essential biochemical processes. We conclude that condensate-related organization principles are ubiquitously used across organisms from bacteria to mammals, and they potentially played a key role in prebiotic evolution, serving as primitive compartments for early biochemical processes.
@article{Hadarovich9033,
author={Anna Hadarovich, David Kuster, Maria Luisa Romero Romero, Agnes Toth-Petroczy},
title={On the Evolution of Biomolecular Condensates: From Prebiotic Origins to Subcellular Diversity.},
journal ={Annual review of cell and developmental biology},
volume={41},
issue ={1},
pages={403--432},
year=2025
}
* joint first authors, # joint corresponding authors