@unpublished{18144, abstract = {High kinetic inductance superconductors are gaining increasing interest for the realisation of qubits, amplifiers and detectors. Moreover, thanks to their high impedance, quantum buses made of such materials enable large zero-point fluctuations of the voltage, boosting the coupling rates to spin and charge qubits. However, fully exploiting the potential of disordered or granular superconductors is challenging, as their inductance and, therefore, impedance at high values are difficult to control. Here we have integrated a granular aluminium resonator, having a characteristic impedance exceeding the resistance quantum, with a germanium double quantum dot and demonstrate strong charge-photon coupling with a rate of $g_\text{c}/2\pi= (566 \pm 2)$ MHz. This was achieved due to the realisation of a wireless ohmmeter, which allows \emph{in situ} measurements during film deposition and, therefore, control of the kinetic inductance of granular aluminium films. Reproducible fabrication of circuits with impedances (inductances) exceeding 13 k$\Omega$ (1 nH per square) is now possible. This broadly applicable method opens the path for novel qubits and high-fidelity, long-distance two-qubit gates.}, author = {Janik, Marian and Roux, Kevin Etienne Robert and Borja Espinosa, Carla N and Sagi, Oliver and Baghdadi, Abdulhamid and Adletzberger, Thomas and Calcaterra, Stefano and Botifoll, Marc and Manjón, Alba Garzón and Arbiol, Jordi and Chrastina, Daniel and Isella, Giovanni and Pop, Ioan M. and Katsaros, Georgios}, booktitle = {arXiv}, title = {{Strong charge-photon coupling in planar germanium enabled by granular aluminium superinductors}}, doi = {10.48550/arXiv.2407.03079}, year = {2024}, } @article{14843, abstract = {The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.}, author = {Chen, JingJing and Kaufmann, Walter and Chen, Chong and Arai, Itaru and Kim, Olena and Shigemoto, Ryuichi and Jonas, Peter M}, issn = {1097-4199}, journal = {Neuron}, number = {5}, pages = {755--771.e9}, publisher = {Elsevier}, title = {{Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse}}, doi = {10.1016/j.neuron.2023.12.002}, volume = {112}, year = {2024}, } @phdthesis{15101, abstract = {The coupling between presynaptic Ca2+ channels and release sensors is a key factor that determines speed and efficacy of synapse transmission. At some excitatory synapses, channel–sensor coupling becomes tighter during development, and tightening is often associated with a switch in the reliance on different Ca2+ channel subtypes. However, the coupling topography at many synapses remains unknown, and it is unclear how it changes during development. To address this question, we analyzed the coupling configuration at the cerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages, combining biophysical analysis, structural analysis, and modeling. Quantal analysis of BC–PC indicated that release probability decreased, while the number of functional sites increased during development. Although transmitter release persistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects of the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased during development, indicative of tightening of source-sensor coupling. Furthermore, presynaptic action potentials became shorter during development, suggesting reduced efficacy of Ca2+ channel activation. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. The number of functional release sites correlated better with the AZ number early in development, but match better with the Ca2+ channel cluster number at later stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.}, author = {Chen, JingJing}, issn = {2663-337X}, pages = {84}, publisher = {Institute of Science and Technology Austria}, title = {{Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse}}, doi = {10.15479/at:ista:15101}, year = {2024}, } @phdthesis{17881, abstract = {This work can be broadly classified into the study of critical phenomena in a one dimensional array of Josephson junctions. While we study quantum criticality when the array is in thermal equilibrium at zero bias, the non-equilibrium study involves understanding the bistability of the array at a critical non-zero bias. This work furthers our knowledge in understanding quantum critical behaviour at finite temperatures in a one dimensional Josephson array, while also establishing relaxation behaviour dual to that observed in a single Josephson junction. Chapter 1 briefly introduces the model to understand superconductor-insulator phase transition in a one dimensional Josephson array and points out the state of the field from where we started our zero-bias experiments. In this context it discusses the phase-charge duality observed in a Josephson array and its dual hysteretic behaviour to that of a single junction, setting the ground for our non-equilibrium study of the array. Chapter 2 shows the experimental setup and the chip layout of the device we measured. In chapter 3 we show that, unlike the typical quantum-critical broadening scenario, in one dimensional Josephson arrays temperature dramatically shifts the critical region. This shift leads to a regime of superconductivity at high temperature, arising from the melted zero-temperature insulator. Our results quantitatively explain the low-temperature onset of superconductivity in nominally insulating regimes, and the transition to the strongly insulating phase. We further present, to our knowledge, the first understanding of the onset of anomalous-metallic resistance saturation [30]. This work demonstrates a non-trivial interplay between thermal effects and quantum criticality. A practical consequence is that, counterintuitively, the coherence of high-impedance quantum circuits is expected to be stabilized by thermal fluctuations. In chapter 4, we show relaxation oscillations in a current-biased one dimensional array of Josephson junctions. These oscillations are well described by a circuit model, dual to the ordinary Josephson relaxation oscillations [72]. Injection locking these oscillations results in current plateaux. The relaxation step is found to obey a characteristic self-consistent relation, suggesting that it is governed by overheating effects. Chapter 5 describes the various checks and analysis we performed to support our conclusions made in chapters 3 and 4. Finally, chapter 6 describes the nanofabrication steps and the finite element electromagnetic simulations we performed to fabricate our devices.}, author = {Mukhopadhyay, Soham}, isbn = {978-3-99078-043-5}, issn = {2663-337X}, pages = {82}, publisher = {Institute of Science and Technology Austria}, title = {{Thermal effects in one dimensional Josephson chains}}, doi = {10.15479/at:ista:17881}, year = {2024}, } @unpublished{18057, abstract = {We report relaxation oscillations in a one-dimensional array of Josephson junctions. The oscillations are circuit-dual to those ordinarily observed in single junctions. The dual circuit quantitatively accounts for temporal dynamics of the array, including the dependence on biasing conditions. Injection locking the oscillations results in well-developed current plateaux. A thermal model explains the relaxation step of the oscillations.}, author = {Mukhopadhyay, Soham and Lancheros Naranjo, Diego A and Senior, Jorden L and Higginbotham, Andrew P}, booktitle = {arXiv}, title = {{Dual relaxation oscillations in a Josephson junction array}}, doi = {10.48550/arXiv.2408.07829}, year = {2024}, } @article{15084, abstract = {GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca 2+ -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.}, author = {Koppensteiner, Peter and Bhandari, Pradeep and Önal, Hüseyin C and Borges Merjane, Carolina and Le Monnier, Elodie and Roy, Utsa and Nakamura, Yukihiro and Sadakata, Tetsushi and Sanbo, Makoto and Hirabayashi, Masumi and Rhee, JeongSeop and Brose, Nils and Jonas, Peter M and Shigemoto, Ryuichi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, publisher = {National Academy of Sciences}, title = {{GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles}}, doi = {10.1073/pnas.2301449121}, volume = {121}, year = {2024}, } @phdthesis{18531, abstract = {Sex chromosomes and autosomes exhibit very different evolutionary dynamics. The Y chromosome usually degenerates, leaving many X-linked loci hemizygous in males. Since recessive X-linked mutations are always exposed to selection in males, selection is more efficient on the X chromosome than on autosomes on recessive mutations, leading to faster adaptation on the X chromosome than other genomic regions, if beneficial mutations are on average recessive (known as the Faster-X effect). In the presence of the functional, but non-recombining gametolog on the Y (as is often the case in young non-recombining regions), recessive mutations are sheltered from selection on the X chromosome. We model this scenario and show that the efficiency of selection is reduced on diploid X loci due to sheltering by the Y chromosome. Reduced efficiency of selection leads to slower adaptation and increased accumulation of deleterious mutations (Slower-X effect). We extended this model to explore the effect of sex-specific selection on degeneration of sex chromosomes, showing theoretically that male-limited genes degenerate on the X chromosome and female-biased genes degenerate on the Y chromosome. This prediction depends on the effective population size and the mutation rate, explaining the variety of sex chromosome degeneration patterns observed in nature. To test for direct evidence of a Slower-X (or Slower-Z) effect, we analyzed the ZW sex chromosomes of the flatworm Schistosoma japonicum, which have a very young non-recombining region with non-degenerated W. Diploid Z-linked genes have higher ratios of non-synonymous to synonymous polymorphisms than autosomal genes, supporting reduced efficiency of selection on the diploid Z region. These results provide evidence of sheltering by the W chromosome, a mechanism that could contribute to Z (X) chromosome degeneration, and illustrate contrasting evolutionary patterns in old and young sex chromosome regions. In addition, genes with sexspecific patterns of expression show opposite patterns of selection in the young (diploid) and old (hemizygous) Z, showing the complex manner in which sex-specific selection shapes the evolutionary patterns of sex chromosomes. }, author = {Mrnjavac, Andrea}, issn = {2663-337X}, keywords = {Sex chromosomes, evolution, selection, sheltering}, pages = {181}, publisher = {Institute of Science and Technology Austria}, title = {{Early stages of sex chromosome evolution}}, doi = {10.15479/at:ista:18531}, year = {2024}, } @phdthesis{18661, abstract = {Across the tree of life, distinct designs of cellular membranes have evolved that are both stable and flexible. In bacteria and eukaryotes this trade-off is accomplished by single-headed lipids that self-assemble into flexible bilayer membranes. By contrast, archaea in many cases possess both bilayer and double-headed, monolayer spanning bolalipids. This composition is believed to enable extremophile archaea to survive harsh environments. Here, through the creation of a minimal computational model for bolalipid membranes, we discover trade-offs when forming membranes using lipids of a single type. Similar to living archaea, we can tune the stiffness of bolalipid molecules. We find that membranes made out of flexible bolalipid molecules resemble bilayer membranes as they can adopt U-shaped conformations to enable higher curvatures. Conversely, rigid bolalipid molecules, like those found in archaea at higher temperatures, preferentially take on a straight conformation to self-assemble into liquid membranes that are stable, stiff, prone to pore formation, and which tear during membrane reshaping. Strikingly, however, our analysis reveals that it is possible to achieve the best of both worlds – membranes that are fluid, stable at high temperatures and flexible enough to be reshaped without leaking – through the inclusion of a small fraction of bilayer lipids into a bolalipid membrane. Additionally, the curvature-dependent softening of bolalipid membranes made of lipids with tension-sensitive conformation can also enable high rigidity at low curvatures while softening at high curvatures, making the membrane effectively a plastic material. Taken together, our study compares the different membrane designs across the tree of life and indicates how combining lipids can be used to resolve trade-offs when generating membranes for (bio)technological applications. }, author = {Santana de Freitas Amaral, Miguel}, isbn = {978-3-99078-046-6}, issn = {2663-337X}, pages = {57}, publisher = {Institute of Science and Technology Austria}, title = {{Archaeal membranes : In silico modelling and design}}, doi = {10.15479/at:ista:18661}, year = {2024}, } @unpublished{18670, abstract = {Across the tree of life, distinct designs of cellular membranes have evolved. In bacteria and eukaryotes single-headed lipids self-assemble into flexible bilayer membranes. By contrast, archaea often possess double-headed, monolayer spanning bolalipids, mixed with bilayer lipids, enabling them to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we discover trade-offs when forming membranes. We find that membranes made out of flexible bolalipids resemble bilayer membranes as bolalipids exhibit conformational switch into U-shaped conformations to enable higher curvatures. Conversely, stiffer bolalipids, resembling those in extremophile archaea, take on straight conformations and form liquid membranes that are stiff, and prone to pore formation during membrane reshaping. Strikingly, we show how to achieve fluid bolalipid membranes that are both stable and flexible – by including small amounts of bilayer lipids, as archaea do. Our study explains how different organisms resolve trade-offs when generating membranes of desired material properties.}, author = {Santana de Freitas Amaral, Miguel and Frey, Felix F and Jiang, Xiuyun and Baum, Buzz and Šarić, Anđela}, booktitle = {bioRxiv}, title = {{Stability vs flexibility: Reshaping archaeal membranes in silico}}, doi = {10.1101/2024.10.18.619072}, year = {2024}, } @unpublished{18549, abstract = {Sex-linked and autosomal loci experience different selective pressures and evolutionary dynamics. X (or Z) chromosomes are often hemizygous, as Y (or W) chromosomes often degenerate. Such hemizygous regions can be under greater efficacy of selection, as recessive mutations are immediately exposed to selection in the heterogametic sex (the so-called Faster-X or Faster-Z effect). However, in young non-recombining regions, Y/W chromosomes often have many functional genes, and many X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on the X/Z by the Y/W homolog is expected to drive a Slower-X (Slower-Z) effect for diploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect has been studied extensively, much less is known empirically about the evolutionary dynamics of diploid X or Z chromosomes. Here, we took advantage of published population genomic data in the female-heterogametic human parasite Schistosoma japonicum to characterize the gene content and diversity levels of the diploid and hemizygous regions of the Z chromosome. We used different metrics of selective pressures acting on genes to test for differences in the efficacy of selection in hemizygous and diploid Z regions, relative to autosomes. We found consistent patterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both hemizygous and diploid Z regions. Moreover, relaxed selection was particularly pronounced for female-biased genes on the diploid Z, as predicted by Slower-Z theory. }, author = {Mrnjavac, Andrea and Vicoso, Beatriz}, booktitle = {bioRxiv}, title = {{Evidence of a Slower-Z effect in Schistosoma japonicum}}, doi = {10.1101/2024.07.02.601697}, year = {2024}, } @phdthesis{18104, abstract = {We introduce a new all-electric platform, that strong couples light to mechanical motion by ensuring that the external environmental coupling dominates over internal mechanical dissipation. The system only has three everyday components: AC, DC, and a fip-chip, in which a metallized silicon nitride membrane is fipped on top of the device under test. This everyday electromechanical device can be operated at low or room temperature and has 10000× lower insertion loss than a comparable commercial quartz crystal, achieves a position imprecision matching state-of-the-art optical interferometer, and enables remote cooling of mechanical motion. The spatial properties of higher order mechanical modes are a promising feature for reconstructing unknown charge distributions. }, author = {Puglia, Denise}, issn = {2663-337X}, pages = {63}, publisher = {Institute of Science and Technology Austria}, title = {{Everyday electromechanics: Capacitive strong coupling to mechanical motion}}, doi = {10.15479/at:ista:18104}, year = {2024}, } @unpublished{18143, abstract = {Strong optomechanical coupling -- a regime where mechanical motion is damped by environmental radiation -- has traditionally required demanding experimental ingredients such as superconducting resonators, high-quality optical cavities, or large magnetic fields. Here we demonstrate a room temperature, cavity-free, all-electric device reaching this regime at radio frequencies, enabled by a mechanically compliant parallel-plate capacitor with a nanoscale plate separation and an aspect ratio exceeding 1,000. The device has four orders of magnitude lower insertion loss than a comparable commercial quartz crystal, and achieves a position imprecision rivaling an optical interferometer. With the help of a back-action isolation scheme, we observe radiative cooling of mechanical motion by a remote cryogenic load. This work provides a technologically accessible route to high-precision sensing, transduction, and signal processing.}, author = {Puglia, Denise and Odessey, Rachel H and Burns, Peter S. and Luhmann, Niklas and Schmid, Silvan and Higginbotham, Andrew P}, booktitle = {arXiv}, title = {{Room temperature, cavity-free capacitive strong coupling to mechanical motion}}, doi = {10.48550/arXiv.2407.15314}, year = {2024}, } @phdthesis{18642, abstract = {This thesis consists of two pieces of work in the broader feld of computational biology, both of which are methods for the analysis of large scale biological data, implemented in efcient software. Chapter 2 introduces a statistical software for causal discovery and inference from observed genetic marker and phenotypic trait data. We explore in simulation how well the method can fne-map genetic efects, fnd the correct causal structure among tens of traits and millions of genetic markers, and infer the causal efect size for the discovered causal relations. We then apply the method to 8 million markers and 17 traits from the UK Biobank and show that many relationships found with other methods are likely due to the efects of hidden confounders. Chapter 3 describes how this method can be applied to longitudinal data. I show how one can incorporate the background knowledge present in the known order of measurements to improve the accuracy of the causal discovery process, and explore the method’s ability to identify age specifc genetic efects, and how the error rates of this recovery are infuenced by missing data due to diferent censoring mechanisms. Chapter 4 introduces a statistical software for the comparison of chromatin contact maps based on the structural similarity index. We explore the robustness of the method to noise and size diferences of the compared maps, show how it can measure evolutionary conservation of topological features by providing a similarity ranking of syntenic regions, and fnally how it can detect alterations in 3D genome structure due to genetic mutations in samples of medical relevance. }, author = {Machnik, Nick N}, issn = {2663-337X}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Algorithms for causal learning and comparative analysis for genomic data}}, doi = {10.15479/at:ista:18642}, year = {2024}, } @unpublished{18648, abstract = {Statistical causal learning in genomics relies on the instrumental variable method of Mendelian Randomization (MR). Currently, an overwhelming number of MR studies purport to show causal relationships among a wide range of risk factors and outcomes. Here, we show that selecting instrument variables from genome-wide association study estimates leads to high false discovery rates for many MR approaches, which can be greatly reduced by employing a graphical inference approach which: (i) explicitly tests instrumental variable assumptions; (ii) distinguishes direct from indirect factors in very high-dimensional data; (iii) discriminates pleiotropic from trait-specific markers, controlling for LD genome-wide; (iv) accommodates rare variants and binary outcomes in a principled way; and (v) identifies potential unobserved latent confounding. For 17 traits and 8.4M variants recorded for 458,747 individuals in the UK Biobank, we show that standard MR analysis gives an abundance of findings that disappear under stringent assumption checks, with many relationships reflecting potential unmeasured confounding. This implies that mixtures of temporal precedence and potential for reverse-causality prohibit understanding the underlying nature of phenotypic and genetic correlations in biobank data. We propose that well-curated longitudinal records are likely needed and that our approach provides a first-step toward robust principled screening for potential causal links. }, author = {Machnik, Nick N and Mahmoudi, Seyed Mahdi and Borczyk, Malgorzata and Krätschmer, Ilse and Bauer, Markus J. and Robinson, Matthew Richard}, booktitle = {bioRxiv}, title = {{Causal inference for multiple risk factors and diseases from genomics data}}, doi = {10.1101/2023.12.06.570392}, year = {2024}, } @phdthesis{18574, abstract = {Biological vision is unlike a camera; rather than transmitting light information faithfully, early visual circuits process the visual scene to convey only the relevant information in an efficient manner. Consequentially, the nature of this visual processing then depends on what is the relevant information in a scene and on the notion of efficiency. In this work, I study how visual processing is modulated by two different variations in the visual scene. First, I discovered that in the mouse (Mus musculus) retina, Retinal Ganglion Cells in the upper and lower visual field have differences in the center surround structure of their receptive fields. Comparison with models of efficient coding show that this adaptation likely evolved to cope with the brightness gradient from the sky to the ground that is pervasive in natural scenes. In the second project, I study how the downstream neurons in the Superior Colliculus dynamically change their temporal selectivity depending on the ambient luminance and behavioral state. As the scene gets darker or when the animal is is less aroused, the neuronal responses get laggier, while still maintaining their relative timing with respect to the population. Overall, this work emphasises the need to understand visual processing in the context of specific demands of the animal in its the environment. The adaptive changes in the visual system, from the retinal ganglion cells to the superior colliculus, highlight the intricate ways in which biological vision optimizes the processing of visual information. }, author = {Gupta, Divyansh}, isbn = {978-3-99078-050-3}, issn = {2663-337X}, pages = {86}, publisher = {Institute of Science and Technology Austria}, title = {{Visual adaptations to natural statistics}}, doi = {10.15479/at:ista:18574}, year = {2024}, } @phdthesis{18471, abstract = {Spatial omics technologies are enriching our understanding of complex biological samples, by allowing us to study their molecular composition while preserving the spatial relationships between molecules in their native context. As the field continues to advance, there are technical challenges that need to be addressed in order to take full advantage of the spatial capabilities of these methods. In this work, I present two technical developments that I established for multiplexed error robust FISH (MERFISH) throughout my PhD: (1) pushing the spatial resolution limits to the nanoscale, and (2) adding rich tissue context to the mouse brain transcriptome. To achieve nanoscale resolution with MERFISH in cultured cells, I combined it with stimulated emission depletion (STED) and expansion microscopy (ExM) to achieve a spatial resolution as low as ~20 nm, and explored the compatibility of MERFISH with singlemolecule localization microscopy (SMLM) techniques. To visualize targeted mRNAs in mouse brain tissue, I applied the comprehensive analysis of tissues across scales (CATS) toolbox, which provides an unbiased morphological readout by labeling the extracellular domain. I successfully established this method, which we call CATS-MERFISH-ExM, to work with thick mouse brain slices, being able to extract transcriptomics information with 3D tissue context. CATS-MERFISH-ExM enabled us to identify cell types and further visualize the subcellular distribution of transcripts in mouse brain tissue, shedding light on the neuropil-specific transcriptome. This method provides integrated information on cellular structure and transcriptomes in situ, and could potentially be applied with other modalities, opening new avenues for scientific discovery. }, author = {Agudelo Duenas, Nathalie}, isbn = {978-3-99078-044-2}, issn = {2663-337X}, pages = {97}, publisher = {Institute of Science and Technology Austria}, title = {{Visualizing the neuronal transcriptional landscape with tissue context}}, doi = {10.15479/at:ista:18471}, year = {2024}, } @article{17148, abstract = {During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable “winning” floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.}, author = {Krammer, Teresa and Stuart, Hannah T. and Gromberg, Elena and Ishihara, Keisuke and Cislo, Dillon and Melchionda, Manuela and Becerril Perez, Fernando and Wang, Jingkui and Costantini, Elena and Rus, Stefanie and Arbanas, Laura and Hörmann, Alexandra and Neumüller, Ralph A. and Elvassore, Nicola and Siggia, Eric and Briscoe, James and Kicheva, Anna and Tanaka, Elly M.}, issn = {1878-1551}, journal = {Developmental Cell}, number = {15}, pages = {1940--1953.e10}, publisher = {Elsevier}, title = {{Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition}}, doi = {10.1016/j.devcel.2024.04.021}, volume = {59}, year = {2024}, } @article{18601, abstract = {Geometrically controlled stem cell differentiation promotes reproducible pattern formation. Here, we present a protocol to fabricate elastomeric stencils for patterned stem cell differentiation. We describe procedures for using photolithography to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils with through holes. We then provide instructions for culturing cells on stencils and, finally, removing stencils to allow colony growth and cell migration. This approach yields reproducible two-dimensional organoids tailored for quantitative studies of growth and pattern formation. For complete details on the use and execution of this protocol, please refer to Lehr et al.1}, author = {Rus, Stefanie and Merrin, Jack and Kulig, Monika Aleksandra and Minchington, Thomas and Kicheva, Anna}, issn = {2666-1667}, journal = {STAR Protocols}, number = {4}, publisher = {Elsevier}, title = {{Protocol for fabricating elastomeric stencils for patterned stem cell differentiation}}, doi = {10.1016/j.xpro.2024.103187}, volume = {5}, year = {2024}, } @article{17890, abstract = {Our understanding of the molecular pathways that regulate oogenesis and define cellular identity in the Arthropod female reproductive system and the extent of their conservation is currently very limited. This is due to the focus on model systems, including Drosophila and Daphnia, which do not reflect the observed diversity of morphologies, reproductive modes, and sex chromosome systems. We use single-nucleus RNA and ATAC sequencing to produce a comprehensive single nucleus atlas of the adult Artemia franciscana female reproductive system. We map our data to the Fly Cell Atlas single-nucleus dataset of the Drosophila melanogaster ovary, shedding light on the conserved regulatory programs between the two distantly related Arthropod species. We identify the major cell types known to be present in the Artemia ovary, including germ cells, follicle cells, and ovarian muscle cells. Additionally, we use the germ cells to explore gene regulation and expression of the Z chromosome during meiosis, highlighting its unique regulatory dynamics and allowing us to explore the presence of meiotic sex chromosome silencing in this group.}, author = {Elkrewi, Marwan N and Vicoso, Beatriz}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {8}, publisher = {Public Library of Science}, title = {{Single-nucleus atlas of the Artemia female reproductive system suggests germline repression of the Z chromosome}}, doi = {10.1371/journal.pgen.1011376}, volume = {20}, year = {2024}, } @article{15009, abstract = {Since the commercialization of brine shrimp (genus Artemia) in the 1950s, this lineage, and in particular the model species Artemia franciscana, has been the subject of extensive research. However, our understanding of the genetic mechanisms underlying various aspects of their reproductive biology, including sex determination, is still lacking. This is partly due to the scarcity of genomic resources for Artemia species and crustaceans in general. Here, we present a chromosome-level genome assembly of A. franciscana (Kellogg 1906), from the Great Salt Lake, United States. The genome is 1 GB, and the majority of the genome (81%) is scaffolded into 21 linkage groups using a previously published high-density linkage map. We performed coverage and FST analyses using male and female genomic and transcriptomic reads to quantify the extent of differentiation between the Z and W chromosomes. Additionally, we quantified the expression levels in male and female heads and gonads and found further evidence for dosage compensation in this species.}, author = {Bett, Vincent K and Macon, Ariana and Vicoso, Beatriz and Elkrewi, Marwan N}, issn = {1759-6653}, journal = {Genome Biology and Evolution}, number = {1}, publisher = {Oxford University Press}, title = {{Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation}}, doi = {10.1093/gbe/evae006}, volume = {16}, year = {2024}, }