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David J Barry, Claudia Gerri, Donald M Bell, Rocco D'Antuono, Kathy K Niakan
GIANI: open-source software for automated analysis of 3D microscopy images.
J Cell Sci, Art. No. jcs.259511 (2022)
Open Access PubMed Source   

The study of cellular and developmental processes in physiologically relevant three-dimensional (3D) systems facilitates an understanding of mechanisms underlying cell fate, disease and injury. While cutting-edge microscopy technologies permit the routine acquisition of 3D datasets, there is currently a limited number of open-source software packages to analyse such images. Here we describe GIANI (General Image Analysis of Nuclei-based Images; https://djpbarry.github.io/Giani), new software for the analysis of 3D images. The design primarily facilitates segmentation of nuclei and cells, followed by quantification of morphology and protein expression. GIANI enables routine and reproducible batch-processing of large numbers of images and comes with scripting and command line tools. We demonstrate the utility of GIANI by quantifying cell morphology and protein expression in confocal images of mouse early embryos and by segmenting nuclei from light sheet microscopy images of the flour beetle embryo. We also validate the performance of the software using simulated data. More generally, we anticipate that GIANI will be a useful tool for researchers in a variety of biomedical fields.
@article{Barry8347,
author={David J Barry, Claudia Gerri, Donald M Bell, Rocco D'Antuono, Kathy K Niakan},
title={GIANI: open-source software for automated analysis of 3D microscopy images.},
journal ={Journal of cell science},
volume={},
pages={null--null},
year=2022
}

Michele Gabriele✳︎, Hugo B Brandão✳︎, Simon Grosse-Holz✳︎, Asmita Jha, Gina M Dailey, Claudia Cattoglio, Tsung-Han S Hsieh, Leonid Mirny, Christoph Zechner#, Anders S Hansen#
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.
Science, 376(6592) 496-501 (2022)
PubMed Source   

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the Fbn2 loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.5% and a median loop lifetime of approximately 10 to 30 minutes. Our results establish that the Fbn2 TAD is highly dynamic, and about 92% of the time, cohesin-extruded loops exist within the TAD without bridging both CTCF boundaries. This suggests that single CTCF boundaries, rather than the fully CTCF-CTCF looped state, may be the primary regulators of functional interactions.
@article{Gabriele8335,
author={Michele Gabriele, Hugo B Brandão, Simon Grosse-Holz, Asmita Jha, Gina M Dailey, Claudia Cattoglio, Tsung-Han S Hsieh, Leonid Mirny, Christoph Zechner, Anders S Hansen},
title={Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.},
journal ={Science (New York, N.Y.)},
volume={376},
issue ={6592},
pages={496--501},
year=2022
}

Suhrid Ghosh#, Weihua Leng, Michaela Wilsch-Bräuninger, Mariana Barrera-Velázquez, Pierre Léopold#, Suzanne Eaton
A local insulin reservoir in Drosophila alpha cell homologs ensures developmental progression under nutrient shortage.
Curr Biol, 32(8) 1788-1797 (2022)
PubMed Source   

Insulin/insulin-like growth factor (IGF) signaling (IIS) controls many aspects of development and physiology. In Drosophila, a conserved family of insulin-like peptides called Dilps is produced by brain neurosecretory cells, and it regulates organismal growth and developmental timing. To accomplish these systemic functions, the Dilps are secreted into the general circulation, and they signal to peripheral tissues in an endocrine fashion. Here, we describe the local uptake and storage of Dilps in the corpora cardiaca (CC), an endocrine organ composed of alpha cell homologs known to produce the glucagon-like adipokinetic hormone (AKH). We show that Dilp uptake by the CC relies on the expression of an IGF-binding protein called ImpL2. Following their uptake, immunogold staining demonstrates that Dilps are co-packaged with AKH in dense-core vesicles for secretion. In response to nutrient shortage, this specific Dilp reservoir is released and activates IIS in a paracrine manner in the prothoracic gland. This stimulates the production of the steroid hormone ecdysone and initiates entry into pupal development. We therefore uncover a sparing mechanism whereby insulin stores in CC serve to locally activate IIS and the production of ecdysone in the PG, accelerating developmental progression in adverse food conditions.
@article{Ghosh8327,
author={Suhrid Ghosh, Weihua Leng, Michaela Wilsch-Bräuninger, Mariana Barrera-Velázquez, Pierre Léopold, Suzanne Eaton},
title={A local insulin reservoir in Drosophila alpha cell homologs ensures developmental progression under nutrient shortage.},
journal ={Current biology : CB},
volume={32},
issue ={8},
pages={1788--1797},
year=2022
}

Foram M Joshi, Gonzalo Alvarez Viar, Gaia Pigino, Hauke Drechsler#, Stefan Diez#
Fabrication of High Aspect Ratio Gold Nanowires within the Microtubule Lumen.
Nano Lett, Art. No. doi: 10.1021/acs.nanolett.2c00255 (2022)
PubMed Source   

Gold nanowires have great potential use as interconnects in electronic, photonic, and optoelectronic devices. To date, there are various fabrication strategies for gold nanowires, each one associated with particular drawbacks as they utilize high temperatures, toxic chemicals, or expensive compounds to produce nanowires of suboptimal quality. Inspired by nanowire fabrication strategies that used higher-order biopolymer structures as molds for electroless deposition of gold, we here report a strategy for the growth of gold nanowires from seed nanoparticles within the lumen of microtubules. Luminal targeting of seed particles occurs through covalently linked Fab fragments of an antibody recognizing the acetylated lysine 40 on the luminal side of α-tubulin. Gold nanowires grown by electroless deposition within the microtubule lumen exhibit a homogeneous morphology and high aspect ratios with a mean diameter of 20 nm. Our approach is fast, simple, and inexpensive and does not require toxic chemicals or other harsh conditions.
@article{Joshi8336,
author={Foram M Joshi, Gonzalo Alvarez Viar, Gaia Pigino, Hauke Drechsler, Stefan Diez},
title={Fabrication of High Aspect Ratio Gold Nanowires within the Microtubule Lumen.},
journal ={Nano letters},
volume={},
pages={null--null},
year=2022
}

Wouter Masselink, Tatiana Sandoval-Guzmán, Maximina H Yun
Meeting report: Salamander Models in Cross-disciplinary Biological Research Meeting.
Dev Dyn, Art. No. doi: 10.1002/dvdy.481 (2022)
Open Access PubMed Source   

The 3rd annual meeting on 'Salamander Models in Cross-disciplinary Biological Research' took place online on August 2021, bringing together over 200 international researchers using salamanders as research models and encompassing diverse fields, ranging from Development and Regeneration through to Immunology, Pathogenesis and Evolution. The event was organized by Maximina H. Yun (Center for Regenerative Therapies Dresden, Germany) and Tatiana Sandoval-Guzmán (TU Dresden, Germany) with the generous support of the Deutsche Forschungsgemeinschaft, the Center for Regenerative Therapies Dresden, Technische Universität Dresden, and the Company of Biologists. Showcasing a number of emerging salamander models, innovative techniques and resources, and providing a platform for sharing both published and ongoing research, this meeting proved to be an excellent forum for exchanging ideas and moving research forwards. Here, we discuss the highlights stemming from this exciting scientific event. This article is protected by copyright. All rights reserved.
@article{Masselink8337,
author={Wouter Masselink, Tatiana Sandoval-Guzmán, Maximina H Yun},
title={Meeting report: Salamander Models in Cross-disciplinary Biological Research Meeting.},
journal ={Developmental dynamics : an official publication of the American Association of Anatomists},
volume={},
pages={null--null},
year=2022
}

Tzer Han Tan✳︎, Jifeng Liu✳︎, Anne Grapin-Botton
Mapping and exploring the organoid state space using synthetic biology.
Semin Cell Dev Biol, Art. No. doi: 10.1016/j.semcdb.2022.04.015 (2022)
PubMed Source   

The functional relevance of an organoid is dependent on the differentiation, morphology, cell arrangement and biophysical properties, which collectively define the state of an organoid. For an organoid culture, an individual organoid or the cells that compose it, these state variables can be characterised, most easily by transcriptomics and by high-content image analysis. Their states can be compared to their in vivo counterparts. Current evidence suggests that organoids explore a wider state space than organs in vivo due to the lack of niche signalling and the variability of boundary conditions in vitro. Using data-driven state inference and in silico modelling, phase diagrams can be constructed to systematically sort organoids along biochemical or biophysical axes. These phase diagrams allow us to identify control strategies to modulate organoid state. To do so, the biochemical and biophysical environment, as well as the cells that seed organoids, can be manipulated.
@article{Tan8339,
author={Tzer Han Tan, Jifeng Liu, Anne Grapin-Botton},
title={Mapping and exploring the organoid state space using synthetic biology.},
journal ={Seminars in cell & developmental biology},
volume={},
pages={null--null},
year=2022
}

Alastair W Skeffington#, Marc Gentzel, Andre Ohara, Alexander Milentyev, Christoph Heintze, Lorenz Böttcher, Stefan Görlich, Andrej Shevchenko, Nicole Poulsen, Nils Kröger#
Shedding light on silica biomineralization by comparative analysis of the silica-associated proteomes from three diatom species.
Plant J, Art. No. doi: 10.1111/tpj.15765 (2022)
PubMed Source   

Morphogenesis of the intricate patterns of diatom silica cell walls is a protein-guided process, yet to date only very few such silica biomineralization proteins have been identified. Therefore, it is currently unknown whether all diatoms share conserved proteins of a basal silica forming machinery, and whether unique proteins are responsible for the morphogenesis of species-specific silica patterns. To answer these questions, we extracted proteins from the silica of three diatom species (Thalassiosira pseudonana, Thalassiosira oceanica and Cyclotella cryptica) by complete demineralization of the cell walls. LC-MS/MS analysis of the extracts identified 92 proteins that we name 'Soluble Silicome Proteins' (SSPs). Surprisingly, no SSPs are common to all three species, and most SSPs showed very low similarity to one another in sequence alignments. In depth bioinformatics analyses revealed that SSPs can be grouped into distinct classes based on short unconventional sequence motifs whose functions are yet unknown. The results from in vivo localization of selected SSPs indicates that proteins, which lack sequence homology but share unconventional sequence motifs may exert similar functions in the morphogenesis of the diatom silica cell wall.
@article{Skeffington8329,
author={Alastair W Skeffington, Marc Gentzel, Andre Ohara, Alexander Milentyev, Christoph Heintze, Lorenz Böttcher, Stefan Görlich, Andrej Shevchenko, Nicole Poulsen, Nils Kröger},
title={Shedding light on silica biomineralization by comparative analysis of the silica-associated proteomes from three diatom species.},
journal ={The Plant journal : for cell and molecular biology},
volume={},
pages={1--1},
year=2022
}

Anne Grapin-Botton#, Barbara Ludwig#
Stem cell-derived β cells go in monkeys.
Cell Stem Cell, 29(4) 500-502 (2022)
PubMed Source   

Du et al. transplanted β cells derived from pluripotent stem cells in diabetic monkeys for the first time, as an intermediate stage toward clinical translation. They observed benefits unfolding over months but also observed immune rejection of the grafts by 5-6 months.
@article{Grapin-Botton8330,
author={Anne Grapin-Botton, Barbara Ludwig},
title={Stem cell-derived β cells go in monkeys.},
journal ={Cell stem cell},
volume={29},
issue ={4},
pages={500--502},
year=2022
}

Akiko Nakamura✳︎, Yan Fung Wong✳︎, Andrea Venturato, Magali Michaut, Seshasailam Venkateswaran, Mithun Santra, Carla A C Gonçalves, Michael Larsen, Marit Leuschner, Yung Hae Kim, Joshua Brickman, Mark Bradley, Anne Grapin-Botton
Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation.
Stem Cell Rep, Art. No. doi: 10.1016/j.stemcr.2022.03.013 (2022)
Open Access PubMed Source   

With the aim of producing β cells for replacement therapies to treat diabetes, several protocols have been developed to differentiate human pluripotent stem cells to β cells via pancreatic progenitors. While in vivo pancreatic progenitors expand throughout development, the in vitro protocols have been designed to make these cells progress as fast as possible to β cells. Here, we report on a protocol enabling a long-term expansion of human pancreatic progenitors in a defined medium on fibronectin, in the absence of feeder layers. Moreover, through a screening of a polymer library we identify a polymer that can replace fibronectin. Our experiments, comparing expanded progenitors to directly differentiated progenitors, show that the expanded progenitors differentiate more efficiently into glucose-responsive β cells and produce fewer glucagon-expressing cells. The ability to expand progenitors under defined conditions and cryopreserve them will provide flexibility in research and therapeutic production.
@article{Nakamura8338,
author={Akiko Nakamura, Yan Fung Wong, Andrea Venturato, Magali Michaut, Seshasailam Venkateswaran, Mithun Santra, Carla A C Gonçalves, Michael Larsen, Marit Leuschner, Yung Hae Kim, Joshua Brickman, Mark Bradley, Anne Grapin-Botton},
title={Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation.},
journal ={Stem cell reports},
volume={},
pages={null--null},
year=2022
}

Kyoohyun Kim✳︎, Vamshidhar Gade✳︎, Teymuras V. Kurzchalia#, Jochen Guck#
Quantitative imaging of Caenorhabditis elegans dauer larvae during cryptobiotic transition.
Biophys J, 121(7) 1219-1229 (2022)
PubMed Source   

Upon starvation or overcrowding, the nematode Caenorhabditis elegans enters diapause by forming a dauer larva, which can then further survive harsh desiccation in an anhydrobiotic state. We have previously identified the genetic and biochemical pathways essential for survival-but without detailed knowledge of their material properties, the mechanistic understanding of this intriguing phenomenon remains incomplete. Here we employed optical diffraction tomography (ODT) to quantitatively assess the internal mass density distribution of living larvae in the reproductive and diapause stages. ODT revealed that the properties of the dauer larvae undergo a dramatic transition upon harsh desiccation. Moreover, mutants that are sensitive to desiccation displayed structural abnormalities in the anhydrobiotic stage that could not be observed by conventional microscopy. Our advance opens a door to quantitatively assessing the transitions in material properties and structure necessary to fully understand an organism on the verge of life and death.
@article{Kim8311,
author={Kyoohyun Kim, Vamshidhar Gade, Teymuras V. Kurzchalia, Jochen Guck},
title={Quantitative imaging of Caenorhabditis elegans dauer larvae during cryptobiotic transition.},
journal ={Biophysical journal},
volume={121},
issue ={7},
pages={1219--1229},
year=2022
}
✳︎ joined first author, # joined corresponding author
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