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Riccardo Maraspini, Chen-Ho Wang, Alf Honigmann
Optimization of 2D and 3D cell culture to study membrane organization with STED microscopy
J Phys D: Appl Phys, 53(1) Art. No. 014001 (2020)
Source   

Epithelia cells assemble into sheets that compartmentalize organs and generate tissue barriers. This is achieved by forming polarized membrane domains, which are connected by junctional complexes. While much is known about the organization of the basal membrane due to its easy accessibility by high and super-resolution microscopy, the apical and lateral membrane domains remain poorly characterized. Here we describe our methods to study the molecular organization of apical and lateral membrane domains by combining 2D and 3D epithelial cell culture with super-resolution STED microscopy. We show that inverted cell monolayers enable live cell imaging of the apical membrane with a resolution sufficient to resolve the densely packed micro-villi of human enterocytes. Furthermore, 3D cell culture enables us to resolve adhesion complexes in the lateral domain of kidney derived cells. We envision that these methods will help to reveal the supra-molecular structure of lateral and apical membrane domains in epithelial cells.
@article{Maraspini7567,
author={Riccardo Maraspini, Chen-Ho Wang, Alf Honigmann},
title={Optimization of 2D and 3D cell culture to study membrane organization with STED microscopy},
journal ={Journal of Physics D: Applied Physics},
volume={53},
issue ={1},
pages={1--1},
year=2020
}

Satu Kujawski, Catia Crespo, Marta Luz, Michaela Yuan, Sylke Winkler, Elisabeth Knust
Loss of Crb2b-lf leads to anterior segment defects in old zebrafish.
Biol Open, Art. No. bio.047555 (2020)
PubMed Source   

Defects in the retina or the anterior segment of the eye lead to compromised vision and affect millions of people. Understanding how these ocular structures develop and are maintained is therefore of paramount importance. The maintenance of proper vision depends, among others, on the function of genes controlling apico-basal polarity. In fact, mutations in polarity genes are linked to retinal degeneration in several species, including human. Here we describe a novel zebrafish crb2b allele (crb2b e40 ), which specifically affects the crb2b long isoform. crb2b e40 mutants are viable and display normal ocular development. However, old crb2b e40 mutant fish develop multiple defects in structures of the anterior segment, which includes the cornea, the iris and the lens. Phenotypes are characterised by smaller pupils due to expansion of the iris and tissues of the iridocorneal angle, an increased number of corneal stromal keratocytes, an abnormal corneal endothelium and an expanded lens capsule. These findings illustrate a novel role for crb2b in the maintenance of the anterior segment and hence add an important function to this polarity regulator, which may be conserved in other vertebrates, including humans.
@article{Kujawski7595,
author={Satu Kujawski, Catia Crespo, Marta Luz, Michaela Yuan, Sylke Winkler, Elisabeth Knust},
title={Loss of Crb2b-lf leads to anterior segment defects in old zebrafish.},
journal ={Biology open},
volume={},
pages={1--1},
year=2020
}

Adam Klosin, F Oltsch, T Harmon, Alf Honigmann, Frank Jülicher, Anthony A. Hyman, Christoph Zechner
Phase separation provides a mechanism to reduce noise in cells.
Science, 367(6476) 464-468 (2020)
PubMed Source   

Expression of proteins inside cells is noisy, causing variability in protein concentration among identical cells. A central problem in cellular control is how cells cope with this inherent noise. Compartmentalization of proteins through phase separation has been suggested as a potential mechanism to reduce noise, but systematic studies to support this idea have been missing. In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control.
@article{Klosin7594,
author={Adam Klosin, F Oltsch, T Harmon, Alf Honigmann, Frank Jülicher, Anthony A. Hyman, Christoph Zechner},
title={Phase separation provides a mechanism to reduce noise in cells.},
journal ={Science (New York, N.Y.)},
volume={367},
issue ={6476},
pages={464--468},
year=2020
}

Simone Fietz, Takashi Namba, Holger Kirsten, Wieland Huttner, Robert Lachmann
Signs of reduced basal progenitor levels and cortical neurogenesis in human foetuses with open spina bifida at 11-15 weeks of gestation.
J Neurosci, Art. No. doi: 10.1523/JNEUROSCI.0192-19.2019 (2020)
PubMed Source   

Open spina bifida (OSB) is one of the most prevalent congenital malformations of the central nervous system that often leads to severe disabilities. Previous studies reported the volume and thickness of the neocortex to be altered in children and adolescents diagnosed with OSB. Until now, the onset and the underlying cause of the atypical neocortex organization in OSB patients remain largely unknown. To examine the effects of OSB on foetal neocortex development, we analysed human foetuses of both sexes diagnosed with OSB between 11-15 weeks of gestation by immunofluorescence for established neuronal and neural progenitor marker proteins and compared the results with healthy controls of the same, or very similar, gestational age. Our data indicate that neocortex development in OSB foetuses is altered as early as 11 weeks of gestation. We observed a marked reduction in the radial thickness of the OSB neocortex, which appears to be attributable to a massive decrease in the number of deep- and upper-layer neurons per field, and found a marked reduction in the number of basal progenitors (BPs) per field in the OSB neocortex, consistent with an impairment of cortical neurogenesis underlying the neuronal decrease in OSB foetuses. Moreover, our data suggest that the decrease in BP number in the OSB neocortex may be associated with BPs spending a lesser proportion of their cell cycle in M-phase. Together, our findings expand our understanding of the pathophysiology of OSB and support the need for an early foetal therapy, i.e. in the first trimester of pregnancy.SIGNIFICANCE STATEMENTOpen spina bifida (OSB) is one of the most prevalent congenital malformations of the central nervous system. This study provides novel data on neocortex development of human OSB foetuses. Our data indicate that neocortex development in OSB foetuses is altered as early as 11 weeks of gestation. We observed a marked reduction in the radial thickness of the OSB neocortex, which appears to be attributable a decrease in the number of deep- and upper-layer neurons per field, and found a marked reduction in the number of basal progenitors per field, indicating that impaired neurogenesis underlies the neuronal decrease in OSB foetuses. Our findings support the need for an early foetal therapy and expand our understanding of the pathophysiology of OSB.
@article{Fietz7590,
author={Simone Fietz, Takashi Namba, Holger Kirsten, Wieland Huttner, Robert Lachmann},
title={Signs of reduced basal progenitor levels and cortical neurogenesis in human foetuses with open spina bifida at 11-15 weeks of gestation.},
journal ={The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume={},
pages={1--1},
year=2020
}

Sean P A Ritter, Allison Lewis, Shelby L Vincent, Li Ling Lo, Ana Margarida da Conceicao Cunha, Danuta Chamot, Ingo Ensminger, George S Espie, George W Owttrim
Evidence for convergent sensing of multiple abiotic stresses in cyanobacteria.
Biochim Biophys Acta Gen Subj, 1864(1) Art. No. 129462 (2020)
PubMed Source   

Bacteria routinely utilize two-component signal transduction pathways to sense and alter gene expression in response to environmental cues. While cyanobacteria express numerous two-component systems, these pathways do not regulate all of the genes within many of the identified abiotic stress-induced regulons.
@article{Ritter7572,
author={Sean P A Ritter, Allison Lewis, Shelby L Vincent, Li Ling Lo, Ana Margarida da Conceicao Cunha, Danuta Chamot, Ingo Ensminger, George S Espie, George W Owttrim},
title={Evidence for convergent sensing of multiple abiotic stresses in cyanobacteria.},
journal ={Biochimica et biophysica acta. General subjects},
volume={1864},
issue ={1},
pages={null--null},
year=2020
}

Virag Sharma, Michael Hiller
Losses of human disease-associated genes in placental mammals
NAR Genomics and Bioinformatics, 2(1) Art. No. doi: 10.1093/nargab/lqz012 (2020)
  Source  

@article{Sharma7569,
author={Virag Sharma, Michael Hiller},
title={Losses of human disease-associated genes in placental mammals},
journal ={NAR Genomics and Bioinformatics},
volume={2},
issue ={1},
pages={1--1},
year=2020
}

Yuting Wang, Sebastian Hinz, Ortrud Uckermann, Pia Hönscheid, Witigo von Schönfels, Greta Burmeister, Alexander Hendricks, Jacobo Miranda Ackerman, Gustavo Baretton, Jochen Hampe, Mario Brosch, Clemens Schafmayer, Andrej Shevchenko, Sebastian Zeissig
Shotgun lipidomics-based characterization of the landscape of lipid metabolism in colorectal cancer.
Biochim Biophys Acta Mol Cell Biol Lipids, 1865(3) Art. No. 158579 (2020)
PubMed Source   

Solid tumors are characterized by global metabolic alterations which contribute to their growth and progression. Altered gene expression profiles and plasma lipid composition suggested a role for metabolic reprogramming in colorectal cancer (CRC) development. However, a conclusive picture of CRC-associated lipidome alterations in the tumor tissue has not emerged. Here, we determined molar abundances of 342 species from 20 lipid classes in matched biopsies of CRC and adjacent normal mucosa. We demonstrate that in contrast to previous reports, CRC shows a largely preserved lipidome composition that resembles that of normal colonic mucosa. Important exceptions include increased levels of lyso-phosphatidylinositols in CRC and reduced abundance of ether phospholipids in advanced stages of CRC. As such, our observations challenge the concept of widespread alterations in lipid metabolism in CRC and rather suggest changes in the cellular lipid profile that are limited to selected lipids involved in signaling and the scavenging of reactive oxygen species.
@article{Wang7575,
author={Yuting Wang, Sebastian Hinz, Ortrud Uckermann, Pia Hönscheid, Witigo von Schönfels, Greta Burmeister, Alexander Hendricks, Jacobo Miranda Ackerman, Gustavo Baretton, Jochen Hampe, Mario Brosch, Clemens Schafmayer, Andrej Shevchenko, Sebastian Zeissig},
title={Shotgun lipidomics-based characterization of the landscape of lipid metabolism in colorectal cancer.},
journal ={Biochimica et biophysica acta. Molecular and cell biology of lipids},
volume={1865},
issue ={3},
pages={null--null},
year=2020
}

Paulo Caldas, Mar López-Pelegrín, Daniel J G Pearce, Nazmi Burak Budanur, Jan Brugués, Martin Loose
Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA.
Nat Commun, 10(1) Art. No. 5744 (2019)
PubMed Source   

During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.
@article{Caldas7573,
author={Paulo Caldas, Mar López-Pelegrín, Daniel J G Pearce, Nazmi Burak Budanur, Jan Brugués, Martin Loose},
title={Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA.},
journal ={Nature communications},
volume={10},
issue ={1},
pages={null--null},
year=2019
}

Gopi Shah, Konstantin Thierbach, Benjamin Schmid, Jens Waschke, Anna Reade, Mario Hlawitschka, Ingo Roeder, Nico Scherf, Jan Huisken
Multi-scale imaging and analysis identify pan-embryo cell dynamics of germlayer formation in zebrafish.
Nat Commun, 10(1) Art. No. 5753 (2019)
PubMed Source   

The coordination of cell movements across spatio-temporal scales ensures precise positioning of organs during vertebrate gastrulation. Mechanisms governing such morphogenetic movements have been studied only within a local region, a single germlayer or in whole embryos without cell identity. Scale-bridging imaging and automated analysis of cell dynamics are needed for a deeper understanding of tissue formation during gastrulation. Here, we report pan-embryo analyses of formation and dynamics of all three germlayers simultaneously within a developing zebrafish embryo. We show that a distinct distribution of cells in each germlayer is established during early gastrulation via cell movement characteristics that are predominantly determined by their position in the embryo. The differences in initial germlayer distributions are subsequently amplified by a global movement, which organizes the organ precursors along the embryonic body axis, giving rise to the blueprint of organ formation. The tools and data are available as a resource for the community.
@article{Shah7574,
author={Gopi Shah, Konstantin Thierbach, Benjamin Schmid, Jens Waschke, Anna Reade, Mario Hlawitschka, Ingo Roeder, Nico Scherf, Jan Huisken},
title={Multi-scale imaging and analysis identify pan-embryo cell dynamics of germlayer formation in zebrafish.},
journal ={Nature communications},
volume={10},
issue ={1},
pages={null--null},
year=2019
}

Gema Gómez-Mariano, Nerea Matamala, Selene Martínez, Iago Justo, Alberto Marcacuzco, Carlos Jimenez, Sara Monzón, Isabel Cuesta, Cristina Garfia, María Teresa Martínez, Meritxell Huch, Ignacio Pérez de Castro, Manuel Posada, Sabina Janciauskiene, Beatriz Martínez-Delgado
Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease.
Hepatol Int, Art. No. doi: 10.1007/s12072-019-10007-y (2019)
PubMed Source   

Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases.
@article{Gómez-Mariano7582,
author={Gema Gómez-Mariano, Nerea Matamala, Selene Martínez, Iago Justo, Alberto Marcacuzco, Carlos Jimenez, Sara Monzón, Isabel Cuesta, Cristina Garfia, María Teresa Martínez, Meritxell Huch, Ignacio Pérez de Castro, Manuel Posada, Sabina Janciauskiene, Beatriz Martínez-Delgado},
title={Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease.},
journal ={Hepatology international},
volume={},
pages={1--1},
year=2019
}