Biology subjects

Richter, S.

Publications and source records attributed to Richter, S..

At least 19 recordsLinked to original sources

bioRxiv2026

ERECTA signaling controls the timing of Arabidopsis Guard Cell maturation at the embryonic leaf tip

While cell identities are established early during embryogenesis, these cells remain immature until germination, and the mechanisms enforcing this developmental pause are poorly understood. Embryonic stomatal cells provide a model to study this pause as the stomatal transcription factor FAMA, normally sufficient for Guard Cell maturation in seedlings, can not drive maturation in the Arabidopsis embryo. Here we show that FAMAs ability to drive maturation depends on leaf polarity and adaxial stomatal cells can progress further in their lineage. We next find that ERECTA-family receptor signaling, which controls stomatal patterning, also suppresses embryonic stomatal maturation. In er erl1 erl2 mutants, cell pairs at the cotyledon tip acquire characteristics of maturing guard cells: cell wall reinforcement, pore-associated thickening, and expression of late lineage markers as identified by whole embryo transcriptomics. This precocious maturation however remains incomplete: many GC markers remain absent, and cells lack an open pore and mature vacuoles. Genetic analysis shows that partial maturation requires but is not limited by low levels of FAMA. Restriction of maturation to the cotyledon tip correlates with locally elevated ERECTA-family receptor abundance, while high auxin appears dispensable for this. Finally, we show that EPFL-ER signaling mediates leaf tip Guard Cell size postembryonically as well. Altogether, we identify ERECTA signaling as a local brake on embryonic stomatal cell maturation, discovering another way to push precocious stomatal cell maturation that results in a complex, partially mature cell state that provide insights into the limitations on cell embryonic cell maturation.

plant biology↗

bioRxiv2026

FLASH reduces radiation-induced oral mucositis in a mouse model of Fanconi anemia

Patients with Fanconi anemia (FA) are particularly susceptible to developing squamous cell carcinoma of the head and neck due to impaired DNA repair pathways. However, their hypersensitivity to DNA damaging agents can limit effective treatment with standard radiotherapy due to severe side effects and complications. In pre-clinical models, ultra-rapid FLASH radiotherapy (FLASH) reduces radiation-induced toxicity in normal tissues while maintaining similar tumor control compared to conventional dose rate radiotherapy (CONV). Here, we investigated the safety of FLASH for treatment of the head and neck in a mouse model of FA. 129/Sv wild-type (WT) and Fanca-deficient (Fanca-/-) mice received single-dose oral cavity irradiation with electron beam FLASH or CONV to evaluate radiation-induced toxicity in non-tumor-bearing mice. Fanca WT and Fanca-/- mice were irradiated with 25 and 18 Gy, respectively, of FLASH (190 Gy/sec) or CONV (0.2 Gy/sec), with tongues harvested at 12 hours (hpi) and 10 days (dpi) post-irradiation. At 10 dpi, FLASH-irradiated tongues in both genetic backgrounds demonstrated reduced ulceration at the dorsal tongue surface compared to CONV-irradiated counterparts. Histopathological analysis of the tongue revealed lower mucositis severity scores with decreased epithelial thinning and ulceration in FLASH-irradiated tongues compared to CONV-irradiated ones. Analysis of {gamma}-H2AX foci formation at 12 hpi demonstrated fewer foci in WT mice treated with FLASH compared to CONV, with a similar trend observed in Fanca-/- mice. These findings suggest a potential normal tissue-sparing effect with FLASH and hold important clinical implications for the treatment of patients with Fanconi anemia and head and neck cancers.

cancer biology↗

bioRxiv2026

A conserved transcriptomic model defines metabolic resilience and vulnerability in obesity

BackgroundObesity arises from a complex interplay of genetic and environmental factors, with alterations of transcriptional networks that integrate metabolic, immune, and regulatory pathways. Conventional measures such as body mass index (BMI) quantify body size but fail to capture the molecular heterogeneity underlying divergent metabolic outcomes. We therefore sought to construct a gene expression-based transcriptomic representation of obesity, using BMI as a practical training anchor, and to use this framework to delineate transcriptional programs associated with metabolically healthy and pathogenic obesity, with subsequent projection to mouse transcriptomic data for cross-species validation. MethodsTranscriptome data of human visceral adipose tissue (N= 1,298) were used to derive the transcriptomic BMI model, and genes contributing to the model were functionally annotated by gene set enrichment analysis. The human-trained model was subsequently applied to mouse selection lines (N = 18) with divergent obesity phenotypes. In the human cohort, post hoc stratification into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) groups was performed using a downstream classification framework incorporating observed BMI together with predicted BMI, to assess whether model-derived predicted BMI reflected obesity-related pathophysiologic status. ResultsModel-selected genes were involved in coordinated regulation of lipid metabolism, immune activation, and growth signaling, extending to mitochondrial and translational pathways. Cross-species analyses uncovered conserved metabolic polarization: DU6 mice exhibited lipid-anabolic and inflammatory remodeling, whereas DU6P mice displayed oxidative, mitochondrial, and GH-axis-enriched transcriptional states. In human cohorts, MHO individuals showed upregulation of mitochondrial energetics and protein synthesis, while MUO individuals were characterized by increased autophagy, lipid catabolism, and stress-adaptive signaling on the transcriptional level. Together, these findings define a conserved molecular continuum linking oxidative efficiency to metabolic health and inflammation to metabolic vulnerability. ConclusionsThis integrative transcriptomic framework bridges human and mouse adipose biology to uncover conserved mechanisms underlying obesity phenotypes. By contrasting mitochondrial and translational programs with inflammatory and catabolic pathways, it provides mechanistic insight into metabolic resilience and a foundation for precision approaches to obesity management.

systems biology↗

bioRxiv2025

Phylogenomics supports monophyly of marsupial crustaceans: a journey to direct development

Peracarida (marsupial crustaceans) represent one of the most diverse and ecologically important crustacean groups, yet their evolutionary relationships have long been debated. Here, we present the most comprehensive phylogenomic analysis of Peracarida to date, incorporating the relict taxa Thermosbaenacea, Mictacea, Ingolfiellida, and Spelaeogriphacea for the first time in a phylogenomic framework. Our results robustly confirm peracarid monophyly and recover a well-supported clade uniting Mancoida (Isopoda, Tanaidaca, Cumacea), Mictacea, and Spelaeogriphacea. We propose the new taxon Panmancoida to encompass this expanded lineage defined by shared developmental and morphological traits. The inferred phylogeny further suggests that peracarid evolution involved a transition from an intermediate "pseudodirect" developmental mode to the direct development seen in most lineages. We further show that the shift to extensive brood care within the marsupium, accompanied by the loss of a free-swimming larval stage, may have accelerated rates of molecular evolution across lineages. Together, these findings provide a robust evolutionary framework for this major malacostracan lineage and highlight how key reproductive innovations reshaped the genomic and life-history trajectories of the marsupial crustaceans.

evolutionary biology↗

bioRxiv2025

Transcriptional targets of SPEECHLESS and FAMA control guard cell division and expansion in the late stomatal lineage

Plant tissue development often relies on the specification of cell type initials with stem cell-like properties. These later undergo differentiation, losing division potential and acquiring specific identities and functions. In the stomatal lineage, protodermal cells develop into guard cells (GCs) through the action of bHLH transcription factors (TFs) SPEECHLESS (SPCH), MUTE and FAMA. Existing models support that these regulators act sequentially, but recent evidence indicates that SPCH expression and function are retained in late stomatal cells. Here, we combine transcriptomic and genetic approaches to define SPCHs function during the late stomatal lineage. We show that relative levels and activities of SPCH and FAMA control GC division and expansion. Through cell type-specific TF induction and mRNA sequencing, we identify late-lineage targets of both TFs, and through genetic perturbation of these targets, we demonstrate that their precise temporal regulation is required for proper GC morphology and function. Our findings reveal a previously unrecognized role for SPCH in late stomatal development and support a revised model in which the functions of stomatal bHLHs are not strictly separated in time.

plant biology↗

bioRxiv2025

Cellular dynamics and epidermal specialization during Arabidopsis floral development at single-cell resolution

Cellular specialization underlies the functional diversification of floral organs, yet the regulatory networks driving epidermal differentiation remain poorly understood. Here, we constructed a single-nucleus transcriptomic atlas of developing Arabidopsis thaliana flowers by profiling over 70,000 nuclei. For annotation of single-cell identities and differentiation status, we additionally generated tissue- and stage-specific transcriptomic datasets using nine fluorescent marker lines spanning four floral developmental stages. Guided by this integrative approach, we focused specifically on the floral epidermis at single-cell resolution and resolved 22 transcriptionally distinct epidermal cell populations. Gene regulatory network analyses identified key transcription factors essential for epidermal differentiation, highlighting MYB16 as a central regulator within the petal epidermis. Developmental trajectory and chromatin-binding analyses demonstrated that MYB16 dynamically orchestrates gene expression programs involved in epidermal identity establishment, cuticle biosynthesis, and stress resilience. Moreover, we demonstrate MYB16 interacts with DRMY1, a regulator of organ growth robustness. Complementation assays confirmed the non-redundant role of MYB16 in epidermal cell fate specification, distinct from other MYB transcription factors. This study provides a comprehensive cellular and regulatory framework for floral epidermal specialization, advancing our understanding of how temporal transcriptional dynamics integrate with spatial cell fate decisions during flower development.

molecular biology↗

bioRxiv2025

Evolutionary origin and functional diversification of plant GBF1-type ARF guanine-nucleotide exchange factors

Large ARF GTPase-activating guanine-nucleotide exchange factors (ARF-GEFs) are essential regulators of membrane trafficking across the eukaryotes. Although conserved, the GBF1-type ARF-GEFs underwent plant-specific evolution. Of the 3 paralogs in Arabidopsis thaliana, AtGNOM-LIKE1 (AtGNL1) performs the GBF1 task of retrograde Golgi-ER traffic whereas AtGNOM mediates polar recycling from endosomes to the basal plasma membrane. AtGNL2 is specific to pollen and is functionally equivalent to AtGNOM. To clarify their evolutionary origin and functional diversification in the plant lineage, we established a phylogenetic tree and ortho-synteny groups (OSGs), which enabled identification of AtGNOM and AtGNL1 orthologs. In addition, somatic paralogs from several species were functionally analysed in transgenic Arabidopsis plants and tested for GNOM-specific DCB-DCB domain interaction in yeast two-hybrid assays. Our results support the following scenario. The ancient plant-specific GBF1-type ARF-GEF was functionally equivalent to AtGNOM and mediated both polar recycling and secretory trafficking. GNL2 only arose in the early flowering plants and then evolved independently. Genome duplication in the basal eudicots - but neither in monocots nor in magnoliids - gave rise to the AtGNL1 ortholog, distinguished by its unique OSG. The AtGNL1 ortholog lost the ability of DCB-DCB interaction and was free to evolve independently, eventually acquiring AtGNL1 function in the rosid clade of core eudicots. In eudicot evolution, the AtGNOM ortholog underwent repeated transposition to different OSGs whereas the AtGNL1 ortholog was recurrently lost but eventually positively selected. This evolutionary process uncoupled polar recycling required for gravitropic response or lateral root initiation from secretory trafficking required for growth.

plant biology↗

bioRxiv2024

ArchMap: A web-based platform for reference-based analysis of single-cell datasets

Leveraging single cell reference atlases to analyse new data has brought about a paradigm shift in single cell data science akin to the first reference genome in genomics. However methods to perform this mapping require computational expertise as well as sometimes considerable compute power, and thus may exclude the researchers from this innovation who may benefit the most from it. ArchMap, a no-code query-to-reference mapping tool, removes this barrier by providing all-in-one automated mapping, cell type annotation, and collaborative features to analyse single-cell datasets from a wide range of integrated, often published, reference atlases and allows extension of atlases with the growing Human Cell Atlas and related efforts. This paves the way for a democratisation of reference mapping capabilities.

bioinformatics↗

bioRxiv2024

Declining juvenile survival of Adelie penguins in Antarctica

As summer sea ice around Antarctica reaches modern lows, quantifying the demographic response of polar species to such environmental changes becomes critical. To achieve this, synthesizing results across species ranges and elucidating the environmental factors driving population dynamics are key. Adelie penguins are considered reliable indicators of changes in Antarctica but the processes through which sea ice and other environmental factors shape their population dynamics are still unclear, especially for critical age groups such as juveniles. Using a 17-year dataset of Adelie penguins electronically tagged in Adelie Land (Antarctica), we found that juvenile survival probability was most impacted by sea ice concentration near their natal colony right after fledging, with lower ice concentrations detrimental to survival. Importantly, we found that juvenile survival declined by 32% from 2007 to 2020, mirroring trends at other distant colonies. The emergence of similar patterns at opposite ends of the continent may be an early signal for shifts in population trends expected from climate change.

ecology↗

bioRxiv2024

Mapping the human hematopoietic stem and progenitor cell hierarchy through integrated single-cell proteomics and transcriptomics

Single-cell transcriptomics (scRNA-seq) has enabled the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, since proteins are the main functional entities in cells, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leverage recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate the first scp-MS dataset of an in vivo differentiation hierarchy encompassing over 2,500 human CD34+ hematopoietic stem and progenitor cells. Through integration with scRNA-seq, we identify proteins that are important for stem cell quiescence, which were not indicated by their mRNA transcripts, and demonstrate functional expression covariance during differentiation that is only detectable on protein level. Finally, we show that modeling translation dynamics can infer cell progression during differentiation and explain 45% more protein variation from mRNA than linear correlation. Our work serves as a framework for future single-cell multi-omics studies across biological systems.

cell biology↗

bioRxiv2024

The iMab antibody selectively binds to intramolecular and intermolecular i-motif structures

i-Motifs are quadruplex nucleic acid conformations that form in cytosine-rich regions. Because of their acidic pH dependence, iMs were thought to form only in vitro. The recent development of an iM-selective antibody, iMab, has allowed iM detection in cells, which revealed their presence at gene promoters and their cell cycle dependence. However, recently evidence emerged which seemed to suggest that iMab recognizes C-rich sequences regardless of their iM conformation. To further investigate the selectivity of iMab, we examined the binding of iMab to C-rich sequences, using a combination of pull-down and Western blot assays. Here we observe that the composition of buffers used during binding and washing steps strongly influences the selectivity of antibody binding. In addition, we demonstrate by NMR that several of the previously reported C-rich sequences, which were not expected to form iMs, actually form intermolecular iMs which are selectively recognized by iMab. Our results highlight the specificity of the iMab antibody, emphasize the importance of optimizing DNA concentrations, blocking and washing conditions, and confirm iMab selectivity not only for intramolecular iMs, but also for intermolecular iMs.

genetics↗

bioRxiv2023

Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons

Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intra-mitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.

neuroscience↗

bioRxiv2023

Coastal marine mammal conservation using thermal imaging-based detection systems

Marine mammal habitats in coastal regions are increasingly threatened as anthropogenic use of these areas increases. Vessel traffic from commercial and pleasure craft leads to increased underwater noise and risk of marine mammal vessel-strike. Mitigation measures advised by competent authorities, such as static and dynamic speed restriction zones or area closures, must be based on reliable data to be justified and find widespread adoption. Thermal detection systems can augment currently employed monitoring approaches such as passive acoustic monitoring or marine mammal observers. Thermal imaging whale detection systems are cost-effective, can be operated around the clock and do not rely on the animal to vocalize, hence have a different availability bias than passive acoustic monitoring. It has been shown in previous studies that thermal detections based on a pronounced blow is possible for larger baleen whales. In this study, we evaluate how effective thermal imaging base whale detection systems are for detecting smaller marine mammals, with a focus on killer whales in Salish Sea.

ecology↗

bioRxiv2023

Remote sensing of emperor penguin abundance and breeding success

Emperor penguins (Aptenodytes forsteri) are under increasing environmental pressure. Monitoring colony size and trends of this Antarctic seabird relies primarily on satellite imagery recorded near the end of the breeding season, when illumination levels are sufficient to capture images, but colony occupancy is highly variable. To correct population estimates for this variability, we develop a phenological model that accurately predicts the number of breeding pairs and fledging chicks, as well as key phenological events such as arrival, hatching and foraging times, from as few as six data points from a single season. The ability to extrapolate occupancy from sparse data makes the model particularly useful for monitoring remotely sensed animal colonies where ground-based population estimates are very rare or unavailable. TeaserThe Emperor penguin becomes the Southern Oceans canary in a coal mine through remote sensing its annual breeding success.

ecology↗

bioRxiv2023

A Tyrosine Phospho-switch within the Longin Domain of VAMP721 modulates SNARE functionality

The final step in secretion is membrane fusion facilitated by SNARE proteins that reside in opposite membranes. The formation of a trans-SNARE complex between one R and three Q coiled-coiled SNARE domains drives the final approach of the membranes providing the mechanical energy for fusion. Biological control of this mechanism is exerted by additional domains within some SNAREs. For example, the N-terminal Longin domain (LD) of R-SNAREs (also called Vesicle-associated membrane proteins, VAMPs) can fold back onto the SNARE domain blocking interaction with other cognate SNAREs. The LD may also determine the subcellular localization via interaction with other trafficking related proteins. Here, we provide cell-biological and genetic evidence that phosphorylation of the Tyrosine57 residue regulates the functionality of VAMP721. We found that an aspartate mutation mimics phosphorylation, leading to protein instability and subsequent degradation in lytic vacuoles. The mutant SNARE also fails to rescue the defects of vamp721vamp722 loss-of-function lines in spite of its wildtype-like localization within the secretory pathway and the ability to interact with cognate SNARE partners. Most importantly, it imposes a dominant negative phenotype interfering with root growth, normal secretion and cytokinesis in wildtype plants generating large aggregates that mainly contain secretory vesicles. Non-phosphorylatable VAMP721Y57F needs higher gene dosage to rescue double mutants in comparison to native VAMP721 underpinning that phosphorylation modulates SNARE function. We propose a model where a short-lived phosphorylation of Y57 serves as a regulatory step to control VAMP721 activity, favouring its open state and interaction with cognate partners to ultimately drive membrane fusion.

plant biology↗

bioRxiv2023

The tyrosine phosphatase LAR acts as a receptor of the nidogen-tetanus toxin complex

Tetanus toxin is one of the most potent neurotoxins and is the causative agent of tetanus. This neurotoxin binds to the neuromuscular junction and, after internalisation into motor neurons, undergoes long-distance axonal transport and transcytosis into spinal cord inhibitory interneurons. Inside the cytoplasm of interneurons, the catalytic chain of the toxin blocks neurotransmitter release, leading to spastic paralysis. Whilst the effects of tetanus toxin intoxication have been extensively studied, the molecular composition of its receptor complex is still poorly understood. We have previously shown that the extracellular matrix proteins nidogens are essential for binding of the toxin to the neuromuscular junction. In this study, we show that the tyrosine phosphatase LAR interacts with the nidogen-tetanus toxin complex and enables its uptake into motor neurons. Binding of LAR to the toxin complex is mediated by its fibronectin III domains, which we have harnessed to inhibit tetanus toxin entry into motor neurons. Surprisingly, this function of LAR is independent of its role in regulating the neurotrophic activity of the TrkB receptor, which has previously been shown to augment the axonal transport of signalling endosomes containing tetanus neurotoxin. These findings identify a multi-subunit complex acting as a protein receptor for tetanus neurotoxin, and demonstrate a novel endocytic trafficking route for extracellular matrix proteins in neurons. Our study paves the way for dissecting the molecular mechanisms that control the recognition and uptake of physiological ligands and pathological proteins at the neuronal plasma membrane, as well as their targeting to the axonal retrograde pathway for long-distance transport within the nervous system.

cell biology↗

bioRxiv2022

Graph neural networks learn emergent tissue properties from spatial molecular profiles

Tissue phenotypes such as metabolic states, inflammation, and tumor properties are functions of molecular states of cells that constitute the tissue. Recent spatial molecular profiling assays measure tissue architecture motifs in a molecular and often unbiased way and thus can explain some aspects of emergence of these phenotypes. Here, we characterize the ability of graph neural networks to model tissue-level emergent phenotypes based on spatial data by evaluating phenotype prediction across model complexities. First, we show that immune cell dispersion in colorectal tumors, which is known to be predictive of disease outcome, can be captured by graph neural networks. Second, we show that breast cancer tumor classes can be predicted from gene expression alone without spatial information and are thus too simplistic a phenotype to require a complex model of emergence. Third, we show that representation learning approaches for spatial graphs of molecular profiles are limited by overfitting in the prevalent regime of up to 100s of images per study. We address overfitting with within-graph self-supervision and illustrate its promise for tissue representation learning as a constraint for node representations.

bioinformatics↗

bioRxiv2022

Robust dimethyl-based multiplex-DIA workflow doubles single-cell proteome depth via a reference channel

Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput and robustness, a challenge that we address here by a streamlined multiplexed workflow using data-independent acquisition (mDIA). We demonstrate automated and complete dimethyl labeling of bulk or single-cell samples, without losing proteomic depth. In single runs of mammalian cells, a three-plex analysis of tryptic peptides quantified 7,700 proteins per channel. The Lys-N enzyme enables five-plex quantification at MS1 and MS2 level. Because the multiplex channels are quantitatively isolated from each other, mDIA accommodates a reference channel that does not interfere with the target channels. Our algorithm RefQuant takes advantage of this feature and confidently quantifies close to 4,000 proteins in single cells with excellent reproducibility, while our workflow currently allows routine analysis of 80 single cells per day. The concept of a stable proteome still holds at this deeper proteome coverage.

systems biology↗