Sort by
Showing 21 to 30 of 2,331 entries
Show entries

Sarita Hebbar, Kai Schuhmann, Andrej Shevchenko, Elisabeth Knust
Hydroxylated sphingolipid biosynthesis regulates photoreceptor apical domain morphogenesis.
J Cell Biol, 219(12) Art. No. e201911100 (2020)
PubMed Source   

Apical domains of epithelial cells often undergo dramatic changes during morphogenesis to form specialized structures, such as microvilli. Here, we addressed the role of lipids during morphogenesis of the rhabdomere, the microvilli-based photosensitive organelle of Drosophila photoreceptor cells. Shotgun lipidomics analysis performed on mutant alleles of the polarity regulator crumbs, exhibiting varying rhabdomeric growth defects, revealed a correlation between increased abundance of hydroxylated sphingolipids and abnormal rhabdomeric growth. This could be attributed to an up-regulation of fatty acid hydroxylase transcription. Indeed, direct genetic perturbation of the hydroxylated sphingolipid metabolism modulated rhabdomere growth in a crumbs mutant background. One of the pathways targeted by sphingolipid metabolism turned out to be the secretory route of newly synthesized Rhodopsin, a major rhabdomeric protein. In particular, altered biosynthesis of hydroxylated sphingolipids impaired apical trafficking via Rab11, and thus apical membrane growth. The intersection of lipid metabolic pathways with apical domain growth provides a new facet to our understanding of apical growth during morphogenesis.
@article{Hebbar7819,
author={Sarita Hebbar, Kai Schuhmann, Andrej Shevchenko, Elisabeth Knust},
title={Hydroxylated sphingolipid biosynthesis regulates photoreceptor apical domain morphogenesis.},
journal ={The Journal of cell biology},
volume={219},
issue ={12},
pages={null--null},
year=2020
}

Ivona Mateska, Kareena Nanda, Natalie Dye, Vasileia Ismini Alexaki, Suzanne Eaton
Range of SHH signaling in adrenal gland is limited by membrane contact to cells with primary cilia.
J Cell Biol, 219(12) Art. No. e201910087 (2020)
PubMed Source   

The signaling protein Sonic Hedgehog (SHH) is crucial for the development and function of many vertebrate tissues. It remains largely unclear, however, what defines the range and specificity of pathway activation. The adrenal gland represents a useful model to address this question, where the SHH pathway is activated in a very specific subset of cells lying near the SHH-producing cells, even though there is an abundance of lipoproteins that would allow SHH to travel and signal long-range. We determine that, whereas adrenal cells can secrete SHH on lipoproteins, this form of SHH is inactive due to the presence of cosecreted inhibitors, potentially explaining the absence of long-range signaling. Instead, we find that SHH-producing cells signal at short range via membrane-bound SHH, only to receiving cells with primary cilia. Finally, our data from NCI-H295R adrenocortical carcinoma cells suggest that adrenocortical tumors may evade these regulatory control mechanisms by acquiring the ability to activate SHH target genes in response to TGF-β.
@article{Mateska7843,
author={Ivona Mateska, Kareena Nanda, Natalie Dye, Vasileia Ismini Alexaki, Suzanne Eaton},
title={Range of SHH signaling in adrenal gland is limited by membrane contact to cells with primary cilia.},
journal ={The Journal of cell biology},
volume={219},
issue ={12},
pages={1--1},
year=2020
}

Anke Weitzmann, Ronald Naumann, Anne Dudeck, Thomas Zerjatke, Alexander Gerbaulet, Axel Roers
Mast Cells Occupy Stable Clonal Territories in Adult Steady-State Skin.
J. Invest. Dermatol., 140(12) 2433-2441 (2020)
PubMed Source   

Mast cells (MCs) are tissue-resident hematopoietic cells intensely studied for their role as effectors in allergic immune responses. Yolk sac-derived embryonic MCs first populate tissues and are later replaced by definitive MCs. We show that definitive MC progenitors expand locally in skin and form clonal colonies that cover stable territories. In MC-deficient skin, colonies grow by proliferation of MCs at the border of the clonal territory. Clonal growth ceases at common borders of neighboring colonies. In steady state, colony self-renewal is independent of bone marrow contribution, and the clonal architecture remains fixed if not disturbed by skin inflammation. Inflammatory cues increase MC density setpoint, stimulating the influx of new progenitors from the bone marrow as well as proliferation of skin-resident cells. The expanding new arrivals disrespect territories of preexisting MC clones. We conclude that during a limited window early in development, definitive MC precursors efficiently enter the skin, expand, and self-maintain, occupying stable territories. In adulthood, circulating progenitors, excluded from steady-state skin, are recruited only into inflamed skin where they clonally expand alongside proliferating skin-resident MCs, disorganizing the original architecture of clonal territories.
@article{Weitzmann7652,
author={Anke Weitzmann, Ronald Naumann, Anne Dudeck, Thomas Zerjatke, Alexander Gerbaulet, Axel Roers},
title={Mast Cells Occupy Stable Clonal Territories in Adult Steady-State Skin.},
journal ={The Journal of investigative dermatology},
volume={140},
issue ={12},
pages={2433--2441},
year=2020
}

Sven Schreiter, Katerina Vafia, Rico Barsacchi, Stephen H Tsang, Marc Bickle, Marius Ader, Mike Karl, Elly M. Tanaka, Seba Almedawar
A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis.
Stem Cell Reports, Art. No. doi: 10.1016/j.stemcr.2020.10.013 (2020)
PubMed Source   

Phagocytosis is a key function in various cells throughout the body. A deficiency in photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) causes vision loss in inherited retinal diseases and possibly age-related macular degeneration. To date, there are no effective therapies available aiming at recovering the lost phagocytosis function. Here, we developed a high-throughput screening assay based on RPE derived from human embryonic stem cells (hRPE) to reveal enhancers of POS phagocytosis. One of the hits, ramoplanin (RM), reproducibly enhanced POS phagocytosis and ensheathment in hRPE, and enhanced the expression of proteins known to regulate membrane dynamics and ensheathment in other cell systems. Additionally, RM rescued POS internalization defect in Mer receptor tyrosine kinase (MERTK) mutant hRPE, derived from retinitis pigmentosa patient induced pluripotent stem cells. Our platform, including a primary phenotypic screening phagocytosis assay together with orthogonal assays, establishes a basis for RPE-based therapy discovery aiming at a broad patient spectrum.
@article{Schreiter7856,
author={Sven Schreiter, Katerina Vafia, Rico Barsacchi, Stephen H Tsang, Marc Bickle, Marius Ader, Mike Karl, Elly M. Tanaka, Seba Almedawar},
title={A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis.},
journal ={Stem cell reports},
volume={},
pages={1--1},
year=2020
}

Leticia Colyn, Marina Bárcena-Varela, Gloria Álvarez-Sola, M Ujue Latasa, Iker Uriarte, Eva Santamaría, Jose M Herranz, Alvaro Santos-Laso, Maria Arechederra, Mikel Ruiz de Gauna, Patricia Aspichueta, Matteo Canale, Andrea Casadei-Gardini, Maria Francesconi, Simone Carotti, Sergio Morini, Leonard J Nelson, Maria J Iraburu, Chaobo Chen, Bruno Sangro, Jose Jg Marin, Maria L Martinez-Chantar, Jesus M Banales, Robert Arnes, Meritxell Huch, John Patino, Altaf A Dar, Mehdi Nosrati, Julen Oyarzábal, Felipe Prósper, Jesus Urman, Francisco Javier Cubero, Christian Trautwein, Carmen Berasain, Maite G Fernandez-Barrena, Matias A Avila
Dual targeting of G9a and DNMT1 for the treatment of experimental cholangiocarcinoma.
Hepatology, Art. No. doi: 10.1002/hep.31642 (2020)
PubMed Source   

Cholangiocarcinoma (CCA) is a devastating disease often detected at advanced stages when surgery cannot be performed. Conventional and targeted systemic therapies perform poorly and therefore effective drugs are urgently needed. Different epigenetic modifications occur in CCA and contribute to malignancy. Targeting epigenetic mechanisms may thus open new therapeutic opportunities. However, modifications such as DNA and histone methylation often co-exist and cooperate in carcinogenesis. We tested the therapeutic efficacy and mechanism of action of a new class of dual G9a histone-methyltransferase and DNA-methyltransferase 1 (DNMT1) inhibitors.
@article{Colyn7852,
author={Leticia Colyn, Marina Bárcena-Varela, Gloria Álvarez-Sola, M Ujue Latasa, Iker Uriarte, Eva Santamaría, Jose M Herranz, Alvaro Santos-Laso, Maria Arechederra, Mikel Ruiz de Gauna, Patricia Aspichueta, Matteo Canale, Andrea Casadei-Gardini, Maria Francesconi, Simone Carotti, Sergio Morini, Leonard J Nelson, Maria J Iraburu, Chaobo Chen, Bruno Sangro, Jose Jg Marin, Maria L Martinez-Chantar, Jesus M Banales, Robert Arnes, Meritxell Huch, John Patino, Altaf A Dar, Mehdi Nosrati, Julen Oyarzábal, Felipe Prósper, Jesus Urman, Francisco Javier Cubero, Christian Trautwein, Carmen Berasain, Maite G Fernandez-Barrena, Matias A Avila},
title={Dual targeting of G9a and DNMT1 for the treatment of experimental cholangiocarcinoma.},
journal ={Hepatology (Baltimore, Md.)},
volume={},
pages={1--1},
year=2020
}

Allison Lewis, Rashmiparvathi Keshara, Yung Hae Kim, Anne Grapin-Botton
Self-organization of organoids from endoderm-derived cells.
J Mol Med (Berl), Art. No. doi: 10.1007/s00109-020-02010-w (2020)
PubMed Source   

Organoids constitute biological systems which are used to model organ development, homeostasis, regeneration, and disease in vitro and hold promise for use in therapy. Reflecting in vivo development, organoids form from tissue cells or pluripotent stem cells. Cues provided from the media and individual cells promote self-organization of these uniform starting cells into a structure, with emergent differentiated cells, morphology, and often functionality that resemble the tissue of origin. Therefore, organoids provide a complement to two-dimensional in vitro culture and in vivo animal models of development, providing the experimental control and flexibility of in vitro methods with the three-dimensional context of in vivo models, with fewer ethical restraints than human or animal work. However, using organoids, we are only just beginning to understand on the cellular level how the external conditions and signaling between individual cells promote the emergence of cells and structures. In this review, we focus specifically on organoids derived from endodermal tissues: the starting conditions of the cells, signaling mechanisms, and external media that allow the emergence of higher order self-organization.
@article{Lewis7851,
author={Allison Lewis, Rashmiparvathi Keshara, Yung Hae Kim, Anne Grapin-Botton},
title={Self-organization of organoids from endoderm-derived cells.},
journal ={Journal of molecular medicine (Berlin, Germany)},
volume={},
pages={1--1},
year=2020
}

Sascha M Kuhn, André Nadler
Messages across time and space.
Elife, 9 Art. No. e63845 (2020)
PubMed Source   

Compartmentalized oscillations of second messengers affect global cellular signaling.
@article{Kuhn7850,
author={Sascha M Kuhn, André Nadler},
title={Messages across time and space.},
journal ={eLife},
volume={9},
pages={null--null},
year=2020
}

Elisa Maria Rieckhoff, Frederic Berndt, Maria Elsner, Stefan Golfier, Franziska Decker, Keisuke Ishihara, Jan Brugués
Spindle Scaling Is Governed by Cell Boundary Regulation of Microtubule Nucleation.
Curr Biol, Art. No. doi: 10.1016/j.cub.2020.10.093 (2020)
PubMed Source   

Cellular organelles such as the mitotic spindle adjust their size to the dimensions of the cell. It is widely understood that spindle scaling is governed by regulation of microtubule polymerization. Here, we use quantitative microscopy in living zebrafish embryos and Xenopus egg extracts in combination with theory to show that microtubule polymerization dynamics are insufficient to scale spindles and only contribute below a critical cell size. In contrast, microtubule nucleation governs spindle scaling for all cell sizes. We show that this hierarchical regulation arises from the partitioning of a nucleation inhibitor to the cell membrane. Our results reveal that cells differentially regulate microtubule number and length using distinct geometric cues to maintain a functional spindle architecture over a large range of cell sizes.
@article{Rieckhoff7855,
author={Elisa Maria Rieckhoff, Frederic Berndt, Maria Elsner, Stefan Golfier, Franziska Decker, Keisuke Ishihara, Jan Brugués},
title={Spindle Scaling Is Governed by Cell Boundary Regulation of Microtubule Nucleation.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2020
}

Stephan Daetwyler, Carl D. Modes, Reto Fiolka
Fiji plugin for annotating movies with custom arrows.
Biol Open, Art. No. doi: 10.1242/bio.056200 (2020)
PubMed Source   

Annotation of time-lapse data provides an important tool to highlight dynamic processes. Particularly, arrows, circles and arrowheads are useful to pinpoint a specific process, stationary or evolving over time. Here, we describe a user-friendly Fiji plugin to facilitate annotation of movies with arrows, arrowheads and circles. The plugin also enables saving and loading of annotated tracks.
@article{Daetwyler7845,
author={Stephan Daetwyler, Carl D. Modes, Reto Fiolka},
title={Fiji plugin for annotating movies with custom arrows.},
journal ={Biology open},
volume={},
pages={1--1},
year=2020
}

Alexandra B Schroeder, Ellen T A Dobson, Curtis Rueden, Pavel Tomancak, Florian Jug, Kevin W Eliceiri
The ImageJ ecosystem: Open-source software for image visualization, processing, and analysis.
Protein Sci, Art. No. doi: 10.1002/pro.3993 (2020)
PubMed Source   

For decades, biologists have relied on software to visualize and interpret imaging data. As techniques for acquiring images increase in complexity, resulting in larger multidimensional datasets, imaging software must adapt. ImageJ is an open-source image analysis software platform that has aided researchers with a variety of image analysis applications, driven mainly by engaged and collaborative user and developer communities. The close collaboration between programmers and users has resulted in adaptations to accommodate new challenges in image analysis that address the needs of ImageJ's diverse user base. ImageJ consists of many components, some relevant primarily for developers and a vast collection of user-centric plugins. It is available in many forms, including the widely used Fiji distribution. We refer to this entire ImageJ codebase and community as the ImageJ ecosystem. Here we review the core features of this ecosystem and highlight how ImageJ has responded to imaging technology advancements with new plugins and tools in recent years. These plugins and tools have been developed to address user needs in several areas such as visualization, segmentation, and tracking of biological entities in large, complex datasets. Moreover, new capabilities for deep learning are being added to ImageJ, reflecting a shift in the bioimage analysis community towards exploiting artificial intelligence. These new tools have been facilitated by profound architectural changes to the ImageJ core brought about by the ImageJ2 project. Therefore, we also discuss the contributions of ImageJ2 to enhancing multidimensional image processing and interoperability in the ImageJ ecosystem.
@article{Schroeder7846,
author={Alexandra B Schroeder, Ellen T A Dobson, Curtis Rueden, Pavel Tomancak, Florian Jug, Kevin W Eliceiri},
title={The ImageJ ecosystem: Open-source software for image visualization, processing, and analysis.},
journal ={Protein science : a publication of the Protein Society},
volume={},
pages={1--1},
year=2020
}