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Mrityunjoy Kar, Avery D Posey, Furqan Dar, Anthony Hyman#, Rohit V Pappu#
Glycine-Rich Peptides from FUS Have an Intrinsic Ability to Self-Assemble into Fibers and Networked Fibrils.
Biochemistry, Art. No. 10.1021/acs.biochem.1c00501 (2021)
PubMed Source   

Glycine-rich regions feature prominently in intrinsically disordered regions (IDRs) of proteins that drive phase separation and the regulated formation of membraneless biomolecular condensates. Interestingly, the Gly-rich IDRs seldom feature poly-Gly tracts. The protein fused in sarcoma (FUS) is an exception. This protein includes two 10-residue poly-Gly tracts within the prion-like domain (PLD) and at the interface between the PLD and the RNA binding domain. Poly-Gly tracts are known to be highly insoluble, being potent drivers of self-assembly into solid-like fibrils. Given that the internal concentrations of FUS and FUS-like molecules cross the high micromolar and even millimolar range within condensates, we reasoned that the intrinsic insolubility of poly-Gly tracts might be germane to emergent fluid-to-solid transitions within condensates. To assess this possibility, we characterized the concentration-dependent self-assembly for three non-overlapping 25-residue Gly-rich peptides derived from FUS. Two of the three peptides feature 10-residue poly-Gly tracts. These peptides form either long fibrils based on twisted ribbon-like structures or self-supporting gels based on physical cross-links of fibrils. Conversely, the peptide with similar Gly contents but lacking a poly-Gly tract does not form fibrils or gels. Instead, it remains soluble across a wide range of concentrations. Our findings highlight the ability of poly-Gly tracts within IDRs that drive phase separation to undergo self-assembly. We propose that these tracts are likely to contribute to nucleation of fibrillar solids within dense condensates formed by FUS.
@article{Kar8197,
author={Mrityunjoy Kar, Avery D Posey, Furqan Dar, Anthony Hyman, Rohit V Pappu},
title={Glycine-Rich Peptides from FUS Have an Intrinsic Ability to Self-Assemble into Fibers and Networked Fibrils.},
journal ={Biochemistry},
volume={},
pages={null--null},
year=2021
}

Lars Hubatsch, Louise Jawerth, Celina Love, Jonathan Bauermann, Ty Dora Tang, Stefano Bo, Anthony Hyman, Christoph A. Weber
Quantitative theory for the diffusive dynamics of liquid condensates.
Elife, 10 Art. No. e68620 (2021)
Open Access PubMed Source   

Key processes of biological condensates are diffusion and material exchange with their environment. Experimentally, diffusive dynamics are typically probed via fluorescent labels. However, to date, a physics-based, quantitative framework for the dynamics of labeled condensate components is lacking. Here we derive the corresponding dynamic equations, building on the physics of phase separation, and quantitatively validate the related framework via experiments. We show that by using our framework we can precisely determine diffusion coefficients inside liquid condensates via a spatio-temporal analysis of fluorescence recovery after photobleaching (FRAP) experiments. We showcase the accuracy and precision of our approach by considering space- and time-resolved data of protein condensates and two different polyelectrolyte-coacervate systems. Interestingly, our theory can also be used to determine a relationship between the diffusion coefficient in the dilute phase and the partition coefficient, without relying on fluorescence measurements in the dilute phase. This enables us to investigate the effect of salt addition on partitioning and bypasses recently described quenching artifacts in the dense phase. Our approach opens new avenues for theoretically describing molecule dynamics in condensates, measuring concentrations based on the dynamics of fluorescence intensities, and quantifying rates of biochemical reactions in liquid condensates.
@article{Hubatsch8198,
author={Lars Hubatsch, Louise Jawerth, Celina Love, Jonathan Bauermann, Ty Dora Tang, Stefano Bo, Anthony Hyman, Christoph A. Weber},
title={Quantitative theory for the diffusive dynamics of liquid condensates.},
journal ={eLife},
volume={10},
pages={null--null},
year=2021
}

C Shan Xu#, Song Pang, Gleb Shtengel, Andreas Müller, Alex T Ritter, Huxley K Hoffman, Shin-Ya Takemura, Zhiyuan Lu, H. Amalia Pasolli, Nirmala Iyer, Jeeyun Chung, Davis Bennett, Aubrey V Weigel, Melanie Freeman, Schuyler B van Engelenburg, Tobias C Walther, Robert Farese, Jennifer Lippincott-Schwartz, Ira Mellman, Michele Solimena, Harald Hess#
An open-access volume electron microscopy atlas of whole cells and tissues.
Nature, Art. No. 10.1038/s41586-021-03992-4 (2021)
PubMed Source   

Understanding cellular architecture is essential for understanding biology. Electron microscopy (EM) uniquely visualizes cellular structures with nanometre resolution. However, traditional methods, such as thin-section EM or EM tomography, have limitations in that they visualize only a single slice or a relatively small volume of the cell, respectively. Focused ion beam-scanning electron microscopy (FIB-SEM) has demonstrated the ability to image small volumes of cellular samples with 4-nm isotropic voxels1. Owing to advances in the precision and stability of FIB milling, together with enhanced signal detection and faster SEM scanning, we have increased the volume that can be imaged with 4-nm voxels by two orders of magnitude. Here we present a volume EM atlas at such resolution comprising ten three-dimensional datasets for whole cells and tissues, including cancer cells, immune cells, mouse pancreatic islets and Drosophila neural tissues. These open access data (via OpenOrganelle2) represent the foundation of a field of high-resolution whole-cell volume EM and subsequent analyses, and we invite researchers to explore this atlas and pose questions.
@article{Xu8199,
author={C Shan Xu, Song Pang, Gleb Shtengel, Andreas Müller, Alex T Ritter, Huxley K Hoffman, Shin-Ya Takemura, Zhiyuan Lu, H. Amalia Pasolli, Nirmala Iyer, Jeeyun Chung, Davis Bennett, Aubrey V Weigel, Melanie Freeman, Schuyler B van Engelenburg, Tobias C Walther, Robert Farese, Jennifer Lippincott-Schwartz, Ira Mellman, Michele Solimena, Harald Hess},
title={An open-access volume electron microscopy atlas of whole cells and tissues.},
journal ={Nature},
volume={},
pages={null--null},
year=2021
}

Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial
Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.
J Cell Biol, 220(10) Art. No. e202103003 (2021)
Open Access PubMed Source   

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.
@article{Belicova8123,
author={Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial},
title={Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.},
journal ={The Journal of cell biology},
volume={220},
issue ={10},
pages={null--null},
year=2021
}

Sara N. Nagelberg✳︎, Jan F. Totz✳︎, Matthäus Mittasch, Vishnu Sresht, Lukas Zeininger, Timothy M Swager, Moritz Kreysing, Mathias Kolle
Actuation of Janus Emulsion Droplets via Optothermally Induced Marangoni Forces.
Phys Rev Lett, 127(14) Art. No. 144503 (2021)
PubMed Source   

Microscale Janus emulsions represent a versatile material platform for dynamic refractive, reflective, and light-emitting optical components. Here, we present a mechanism for droplet actuation that exploits thermocapillarity. Using optically induced thermal gradients, an interfacial tension differential is generated across the surfactant-free internal capillary interface of Janus droplets. The interfacial tension differential causes droplet-internal Marangoni flows and a net torque, resulting in a predictable and controllable reorientation of the droplets. The effect can be quantitatively described with a simple model that balances gravitational and thermal torques. Occurring in small thermal gradients, these optothermally induced Marangoni dynamics represent a promising mechanism for controlling droplet-based micro-optical components.
@article{Nagelberg8196,
author={Sara N. Nagelberg, Jan F. Totz, Matthäus Mittasch, Vishnu Sresht, Lukas Zeininger, Timothy M Swager, Moritz Kreysing, Mathias Kolle},
title={Actuation of Janus Emulsion Droplets via Optothermally Induced Marangoni Forces.},
journal ={Physical review letters},
volume={127},
issue ={14},
pages={null--null},
year=2021
}

Glyn Nelson✳︎#, Ulrike Boehm✳︎#, Steve Bagley, Peter Bajcsy, Johanna Bischof, Claire M Brown, Aurélien Dauphin, Ian M Dobbie, John E Eriksson, Orestis Faklaris, Julia Fernandez-Rodriguez, Alexia Ferrand, Laurent Gelman, Ali Gheisari, Hella Hartmann, Christian Kukat, Alex Laude, Miso Mitkovski, Sebastian Munck, Alison J North, Tobias Manuel Rasse, Ute Resch-Genger, Lucas C Schuetz, Arne Seitz, Caterina Strambio-De-Castillia, Jason R Swedlow, Ioannis Alexopoulos, Karin Aumayr, Sergiy Avilov, Gert-Jan Bakker, Rodrigo R Bammann, Andrea Bassi, Hannes Beckert, Sebastian Beer, Yury Belyaev, Jakob Bierwagen, Konstantin A Birngruber, Manel Bosch, Juergen Breitlow, Lisa A Cameron, Joe Chalfoun, James J Chambers, Chieh-Li Chen, Eduardo Conde-Sousa, Alexander D Corbett, Fabrice P Cordelieres, Elaine Del Nery, Ralf Dietzel, Frank Eismann, Elnaz Fazeli, Andreas Felscher, Hans-Ulrich Fried, Nathalie Gaudreault, Wah Ing Goh, Thomas Guilbert, Roland Hadleigh, Peter Hemmerich, Gerhard A Holst, Michelle S Itano, Claudia B Jaffe, Helena Jambor, Stuart C Jarvis, Antje Keppler, David Kirchenbuechler, Marcel Kirchner, Norio Kobayashi, Gabriel Krens, Susanne Kunis, Judith Lacoste, Maresca Marcello, Gabriel G Martins, Daniel J Metcalf, Claire A Mitchell, Joshua Moore, Tobias Mueller, Michael S Nelson, Stephen Ogg, Shuichi Onami, Alexandra L Palmer, Perrine Paul-Gilloteaux, Jaime A Pimentel, Laure Plantard, Santosh Podder, Elton Rexhepaj, Arnaud Royon, Markku A Saari, Damien Schapman, Vincent Schoonderwoert, Britta Schroth-Diez, Stanley Schwartz, Michael Shaw, Martin Spitaler, Martin T Stoeckl, Damir Sudar, Jeremie Teillon, Stefan Terjung, Roland Thuenauer, Christian D Wilms, Graham D Wright, Roland Nitschke#
QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.
J Microsc, 284(1) 56-73 (2021)
Open Access PubMed Source   

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
@article{Nelson8102,
author={Glyn Nelson, Ulrike Boehm, Steve Bagley, Peter Bajcsy, Johanna Bischof, Claire M Brown, Aurélien Dauphin, Ian M Dobbie, John E Eriksson, Orestis Faklaris, Julia Fernandez-Rodriguez, Alexia Ferrand, Laurent Gelman, Ali Gheisari, Hella Hartmann, Christian Kukat, Alex Laude, Miso Mitkovski, Sebastian Munck, Alison J North, Tobias Manuel Rasse, Ute Resch-Genger, Lucas C Schuetz, Arne Seitz, Caterina Strambio-De-Castillia, Jason R Swedlow, Ioannis Alexopoulos, Karin Aumayr, Sergiy Avilov, Gert-Jan Bakker, Rodrigo R Bammann, Andrea Bassi, Hannes Beckert, Sebastian Beer, Yury Belyaev, Jakob Bierwagen, Konstantin A Birngruber, Manel Bosch, Juergen Breitlow, Lisa A Cameron, Joe Chalfoun, James J Chambers, Chieh-Li Chen, Eduardo Conde-Sousa, Alexander D Corbett, Fabrice P Cordelieres, Elaine Del Nery, Ralf Dietzel, Frank Eismann, Elnaz Fazeli, Andreas Felscher, Hans-Ulrich Fried, Nathalie Gaudreault, Wah Ing Goh, Thomas Guilbert, Roland Hadleigh, Peter Hemmerich, Gerhard A Holst, Michelle S Itano, Claudia B Jaffe, Helena Jambor, Stuart C Jarvis, Antje Keppler, David Kirchenbuechler, Marcel Kirchner, Norio Kobayashi, Gabriel Krens, Susanne Kunis, Judith Lacoste, Maresca Marcello, Gabriel G Martins, Daniel J Metcalf, Claire A Mitchell, Joshua Moore, Tobias Mueller, Michael S Nelson, Stephen Ogg, Shuichi Onami, Alexandra L Palmer, Perrine Paul-Gilloteaux, Jaime A Pimentel, Laure Plantard, Santosh Podder, Elton Rexhepaj, Arnaud Royon, Markku A Saari, Damien Schapman, Vincent Schoonderwoert, Britta Schroth-Diez, Stanley Schwartz, Michael Shaw, Martin Spitaler, Martin T Stoeckl, Damir Sudar, Jeremie Teillon, Stefan Terjung, Roland Thuenauer, Christian D Wilms, Graham D Wright, Roland Nitschke},
title={QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.},
journal ={Journal of microscopy},
volume={284},
issue ={1},
pages={56--73},
year=2021
}

Fabio Da Silva✳︎, Kaiqing Zhang✳︎, Anneline Pinson, Edoardo Fatti, Michaela Wilsch-Bräuninger, Jessica Herbst, Valerie Vidal, Andreas Schedl, Wieland Huttner#, Christof Niehrs#
Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex.
EMBO J, 40(19) Art. No. e108041 (2021)
Open Access PubMed Source   

The role of WNT/β-catenin signalling in mouse neocortex development remains ambiguous. Most studies demonstrate that WNT/β-catenin regulates progenitor self-renewal but others suggest it can also promote differentiation. Here we explore the role of WNT/STOP signalling, which stabilizes proteins during G2/M by inhibiting glycogen synthase kinase (GSK3)-mediated protein degradation. We show that mice mutant for cyclin Y and cyclin Y-like 1 (Ccny/l1), key regulators of WNT/STOP signalling, display reduced neurogenesis in the developing neocortex. Specifically, basal progenitors, which exhibit delayed cell cycle progression, were drastically decreased. Ccny/l1-deficient apical progenitors show reduced asymmetric division due to an increase in apical-basal astral microtubules. We identify the neurogenic transcription factors Sox4 and Sox11 as direct GSK3 targets that are stabilized by WNT/STOP signalling in basal progenitors during mitosis and that promote neuron generation. Our work reveals that WNT/STOP signalling drives cortical neurogenesis and identifies mitosis as a critical phase for neural progenitor fate.
@article{Silva8168,
author={Fabio Da Silva, Kaiqing Zhang, Anneline Pinson, Edoardo Fatti, Michaela Wilsch-Bräuninger, Jessica Herbst, Valerie Vidal, Andreas Schedl, Wieland Huttner, Christof Niehrs},
title={Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex.},
journal ={The EMBO journal},
volume={40},
issue ={19},
pages={null--null},
year=2021
}

Mark Skamrahl, Hongtao Pang, Maximilian Ferle, Jannis Gottwald, Angela Rübeling, Riccardo Maraspini, Alf Honigmann, Tabea A Oswald, Andreas Janshoff
Tight Junction ZO Proteins Maintain Tissue Fluidity, Ensuring Efficient Collective Cell Migration.
Adv Sci (Weinh), 8(19) Art. No. 2100478 (2021)
Open Access PubMed Source   

Tight junctions (TJs) are essential components of epithelial tissues connecting neighboring cells to provide protective barriers. While their general function to seal compartments is well understood, their role in collective cell migration is largely unexplored. Here, the importance of the TJ zonula occludens (ZO) proteins ZO1 and ZO2 for epithelial migration is investigated employing video microscopy in conjunction with velocimetry, segmentation, cell tracking, and atomic force microscopy/spectroscopy. The results indicate that ZO proteins are necessary for fast and coherent migration. In particular, ZO1 and 2 loss (dKD) induces actomyosin remodeling away from the central cortex towards the periphery of individual cells, resulting in altered viscoelastic properties. A tug-of-war emerges between two subpopulations of cells with distinct morphological and mechanical properties: 1) smaller and highly contractile cells with an outward bulging apical membrane, and 2) larger, flattened cells, which, due to tensile stress, display a higher proliferation rate. In response, the cell density increases, leading to crowding-induced jamming and more small cells over time. Co-cultures comprising wildtype and dKD cells migrate inefficiently due to phase separation based on differences in contractility rather than differential adhesion. This study shows that ZO proteins are necessary for efficient collective cell migration by maintaining tissue fluidity and controlling proliferation.
@article{Skamrahl8134,
author={Mark Skamrahl, Hongtao Pang, Maximilian Ferle, Jannis Gottwald, Angela Rübeling, Riccardo Maraspini, Alf Honigmann, Tabea A Oswald, Andreas Janshoff},
title={Tight Junction ZO Proteins Maintain Tissue Fluidity, Ensuring Efficient Collective Cell Migration.},
journal ={Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume={8},
issue ={19},
pages={null--null},
year=2021
}

Hui Wang, Xiaofei Li, Tetsuhiro Kajikawa, Jieun Shin, Jong-Hyung Lim, Ioannis Kourtzelis, Kosuke Nagai, Jonathan Korostoff, Sylvia Grossklaus, Ronald Naumann, Trian Chavakis, George Hajishengallis
Stromal cell-derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis.
J. Clin. Invest., 131(19) Art. No. e150578 (2021)
PubMed Source   

The secreted protein developmental endothelial locus 1 (DEL-1) regulates inflammatory cell recruitment and protects against inflammatory pathologies in animal models. Here, we investigated DEL-1 in inflammatory arthritis using collagen-induced arthritis (CIA) and collagen Ab-induced arthritis (CAIA) models. In both models, mice with endothelium-specific overexpression of DEL-1 were protected from arthritis relative to WT controls, whereas arthritis was exacerbated in DEL-1-deficient mice. Compared with WT controls, mice with collagen VI promoter-driven overexpression of DEL-1 in mesenchymal cells were protected against CIA but not CAIA, suggesting a role for DEL-1 in the induction of the arthritogenic Ab response. Indeed, DEL-1 was expressed in perivascular stromal cells of the lymph nodes and inhibited Tfh and germinal center B cell responses. Mechanistically, DEL-1 inhibited DC-dependent induction of Tfh cells by targeting the LFA-1 integrin on T cells. Overall, DEL-1 restrained arthritis through a dual mechanism, one acting locally in the joints and associated with the anti-recruitment function of endothelial cell-derived DEL-1; the other mechanism acting systemically in the lymph nodes and associated with the ability of stromal cell-derived DEL-1 to restrain Tfh responses. DEL-1 may therefore be a promising therapeutic for the treatment of inflammatory arthritis.
@article{Wang8156,
author={Hui Wang, Xiaofei Li, Tetsuhiro Kajikawa, Jieun Shin, Jong-Hyung Lim, Ioannis Kourtzelis, Kosuke Nagai, Jonathan Korostoff, Sylvia Grossklaus, Ronald Naumann, Trian Chavakis, George Hajishengallis},
title={Stromal cell-derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis.},
journal ={The Journal of clinical investigation},
volume={131},
issue ={19},
pages={null--null},
year=2021
}

Zahra Ghezelayagh✳︎, Mahsa Zabihi✳︎, Ibrahim Zarkesh, Carla A C Gonçalves, Michael Larsen, Newsha Hagh-Parast, Mohammad Pakzad, Massoud Vosough, Babak Arjmand, Hossein Baharvand, Banafshé Larijani, Anne Grapin-Botton, Hamid Reza Aghayan#, Yaser Tahamtani#
Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional Co-culture System.
Stem Cell Rev Rep, Art. No. 10.1007/s12015-021-10266-z (2021)
PubMed Source   

Mesenchymal cells of diverse origins differ in gene and protein expression besides producing varying effects on their organ-matched epithelial cells' maintenance and differentiation capacity. Co-culture with rodent's tissue-specific pancreatic mesenchyme accelerates proliferation, self-renewal, and differentiation of pancreatic epithelial progenitors. Therefore, in our study, the impact of three-dimensional (3D) co-culture of human fetal pancreatic-derived mesenchymal cells (hFP-MCs) with human embryonic stem cell-derived pancreatic progenitors (hESC-PPs) development towards endocrine and beta cells was assessed. Besides, the ability to maintain scalable cultures combining hFP-MCs and hESC-PPs was investigated. hFP-MCs expressed many markers in common with bone marrow-derived mesenchymal stem cells (BM-MSCs). However, they showed higher expression of DESMIN compared to BM-MSCs. After co-culture of hESC-PPs with hFP-MCs, the pancreatic progenitor (PP) spheroids generated in Matrigel had higher expression of NGN3 and INSULIN than BM-MSCs co-culture group, which shows an inductive impact of pancreatic mesenchyme on hESC-PPs beta-cells maturation. Pancreatic aggregates generated by forced aggregation through scalable AggreWell system showed similar features compared to the spheroids. These aggregates, a combination of hFP-MCs and hESC-PPs, can be applied as an appropriate tool for assessing endocrine-niche interactions and developmental processes by mimicking the pancreatic tissue.
@article{Ghezelayagh8186,
author={Zahra Ghezelayagh, Mahsa Zabihi, Ibrahim Zarkesh, Carla A C Gonçalves, Michael Larsen, Newsha Hagh-Parast, Mohammad Pakzad, Massoud Vosough, Babak Arjmand, Hossein Baharvand, Banafshé Larijani, Anne Grapin-Botton, Hamid Reza Aghayan, Yaser Tahamtani},
title={Improved Differentiation of hESC-Derived Pancreatic Progenitors by Using Human Fetal Pancreatic Mesenchymal Cells in a Micro-scalable Three-Dimensional Co-culture System.},
journal ={Stem cell reviews and reports},
volume={},
pages={null--null},
year=2021
}


✳︎ joined first author, # joined corresponding author