Biology subjects

Jonsson, H.

Publications and source records attributed to Jonsson, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Sex differences in the genetic basis of human recombination within 190,000 parent-child pairs

Structured AbstractO_ST_ABSIntroductionC_ST_ABSSexual reproduction uses a specialized cell division called meiosis, in which a single round of DNA replication is followed by two cell divisions to create hap-loid gametes. Genetic recombination in meiosis assures faithful segregation of chromosomes and establishes patterns of genetic linkage and inheritance. Meiotic recombination is thus a fundamental genomic process that shapes major features of the genomic landscape, influences mutation, and creates genetic diversity. RationaleThe genetic basis of between-individual variation in the occurrence and genomic location of meiotic recombination events remains poorly understood in humans. In particular, we lack an understanding of whether the same DNA regions shape vari-ation in recombination rates across studies. We address this by curating 112,144 maternal and 78,653 paternal meiosis events (parent-child pairs) across cohorts from four countries, creating the largest dataset of its kind. ResultsWe identify 58 independent genomic regions associated with the occurrence and genomic location of recombination events, 24 of which are unique across phe-notypes. Of the 24 unique regions, 6 are novel and specific to female meiotic recombination harboring genes linked to ovarian function, a 7th novel region is linked to male recombination. Many regions have significant sex-dependent ef-fects across studies. We estimate the between-sex genetic correlation for meiotic recombination rate to be 0.374 (0.072 SD), which captures the extent to which the genetic factors influencing a trait in one sex also impact the same trait in the other. 30-40% of the individual-level variation in recombination rate is at-tributable to DNA markers, of which only 37.7% (2.7% SD) and 47.1% (3.8% SD) is attributable to previously known global modulators of meiotic recombi-nation, in females and males respectively. We create a polygenic predictor that significantly predicts recombination rates of both women and men after adjusting for age and year of birth. We find significant correlations between female meiotic recombination, reproductive outcomes and reproductive aging, after adjusting for study ascertainment. ConclusionsIn the largest meta-analysis to date of human meiotic recombination, we identify novel loci with sex-specific effects that influence male and female recombination rate across multiple cohorts.

genomics↗

bioRxiv2026

Robust Organ Shape During Growth Requires Local Morphogen Signaling and Global Curvature Feedback

Precise organ shape during development requires feedback between organ-scale geometry and cell-level growth dynamics. Here, we use the apical hook of dicotyledonous plants as a model to study this multiscale control. This protective structure forms a [~]180{degrees} bend that is stably maintained despite rapid elongation. Combining quantitative growth mapping, multiscale modeling, and hormone analysis, we identify the cellular dynamics underlying hook maintenance. Contrary to the prevailing model, hook stability does not arise from sustained inner-outer growth asymmetry. Instead, stable curvature emerges from a biphasic, self-similar growth pattern that remains spatially fixed despite continuous cell flux. Auxin-driven growth asymmetry induces bending but is spatially restricted and insufficient to maintain shape. By contrast, a graded, auxin-independent autotropic response provides curvature-dependent growth regulation that counteracts bending and stabilizes shape against perturbations. Together, these findings establish a general principle in which local morphogen-driven bending and global geometry-dependent feedback jointly maintain robust organ shape during growth. HighlightsO_LISelf-similar growth maintains apical hook curvature despite continuous cell flux C_LIO_LICurvature stability emerges from coordinated axial and differential growth C_LIO_LIAuxin asymmetry is spatially restricted and insufficient for shape maintenance C_LIO_LICurvature-dependent feedback ensures robust and optimized hook shape C_LI

plant biology↗

bioRxiv2026

Endometriosis lesions are oligoclonal structures derived from the normal endometrium

Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. The origin of this ectopic tissue is debated, with leading theories including retrograde menstruation and embryonic remnants. Using somatic mutations as markers, we show that endometriosis lesions consist of unrelated clones of epithelial cells, with stromal cells being distinct, and that lesions at different body sites have different sets of clones. We observed that mutation burdens, signatures and driver landscapes are similar in cells from lesions and normal endometrium and the distribution of somatic mutations along the length of chromosomes is consistent with uterine origin. Furthermore a large-scale screen of the normal endometrium of endometriosis patients identified clones that are ancestral to endometriosis, indicating that the ectopic tissue in endometriosis originates from the normal endometrium.

genetics↗

bioRxiv2025

Root hair growth phases are coordinated by cytoskeleton, nucleus dynamics and cell mechanics in Arabidopsis

Polar cell growth is a fundamental process across organisms, yet its coordination with nuclear movement and cytoskeleton dynamics remains underexplored. Focusing on Arabidopsis thaliana root hairs, we investigate these processes using high-resolution live imaging within microfluidics-based experiments. By incorporating data on cytoskeletal dynamics, nuclear positioning, and tip growth into a mathematical model, we analyse how their interactions shape the different growth phases that we reveal for the first time in this study. Chemical treatments and mutant analyses further support our model, revealing that timely cytoskeletal changes drive transitions between these growth phases, and correlate with shifts in nuclear movement and morphology. This regulation suggests a microtubule-actin crosstalk in the root hair subapical region. Additionally, we present novel findings on vacuole movement and cell stiffness, further refining our understanding of tip growth dynamics. Collectively, our work provides a comprehensive framework for understanding how transitions between growth phases are orchestrated in plant tip-growing cells.

cell biology↗

bioRxiv2025

Plasticity and invariance of Arabidopsis inflorescence and floral shoot apical meristems in response to mineral nutrients

In many species, floral organ production is invariant while flower production rate can be plastic. This allows plants to adapt flower number to their environment whilst maintaining a constant flower structure. The CLAVATA/WUSCHEL feedback loop underpins both inflorescence (IM) and floral meristem (FM) activity, respectively responsible for flower and floral organ production. We explore how plasticity and invariance can differ between IM and FM in response to nutrient availability. FM size is less sensitive to changes in nutrients than IM size, and floral organ production is insensitive to these small size changes. However, clavata3 mutants display larger changes in FM size, approaching those observed in WT IM under nutrient change, with increased floral organ number. This suggests that invariant floral organ production requires that FM size undergoes limited changes in response to nutrients. Compared to the IM, in the FM, levels of cytokinin (CK) signaling are lower and CK signaling and WUSCHEL expression are less impacted by nutrient level. Through genetic perturbations, we show a reduced response of FMs to varying cytokinin levels. Our work shows one way that the balance between plasticity and invariance can be set differently in different contexts.

plant biology↗

bioRxiv2025

Machine learning segmentation tool trained on synthetic data for tracking cytoskeleton polymerisation and depolymerisation

The cytoskeleton is important in controlling the growth and morphology of plant cells, so tracking its morphological changes is essential. Here, we develop a new machine learning based segmentation tool for microtubules (MTs), which can distinguish between polymerised and depolymerised fibres. To circumvent the low abundance of data, we trained on synthetic images of microtubules from a computational micro-tubule model, pre-processed to reproduce microscope effects and partial depolymerisation. We used this tool to investigate how the MT network in an Arabidopsis thaliana root hair cell repolymerises after depolymerisation under Oryzalin (OZ) drug treatments. Specifically, we show the network initially repolymerises from the shank region. This work demonstrates the viability of using synthetic data to train machine learning systems handling cytoskeletal image data.

plant biology↗

bioRxiv2024

Single-nucleus transcriptomics resolves differentiation dynamics between shoot stem cells and primary stem.

The shoot apical meristem (SAM), located at the plant apex, is accountable for the formation of above-ground organs such as leaves, stem and flowers. Although transcriptional profiling has elucidated some cell-types observed within stems or flowers, the differentiation transcriptional dynamics from shoot stem cells to multiple cell identities remain unknown. We employed a single-nucleus RNA-sequencing approach to assess the transcriptional heterogeneity and cell differentiation processes within the SAM. By collecting dissected inflorescence meristems, we constructed an inflorescence single-nucleus SAM atlas from Arabidopsis thaliana. Our analysis unveiled regulatory elements for most previously known cell types such as the boundary domain, vasculature, early primordia, epidermis and internal stem cells. We also identified previously unobserved transcriptional profiles, revealing that the stem cortex is defined early within forming primordia. Moreover, trajectory inference analysis allowed us to capture spatial control of S-phase machinery by floral homeotic genes and differentiation gene expression dynamics from internal shoot stem cells toward internal layers such as cortex, cambium, xylem and phloem. The results advance our understanding of the cellular and transcriptional heterogeneity underlying the cell-fate transcriptional dynamics shaping shoot organs and architecture.

developmental biology↗

bioRxiv2024

Hibiscus bullseyes reveal mechanisms controlling petal pattern proportions that influence plant-pollinator interactions

Colourful patterns on flower corollas are key signals to attract pollinators. The formation of such motifs relies on the establishment of developmental boundaries that partition the growing petal epidermis into different subdomains, where cells can produce specific pigments and acquire distinctive cell shapes and textures. While some of the transcription factors and biosynthetic pathways producing these characteristics as cell differentiate have been extensively studied, the upstream processes restricting the activities of molecular players to specific regions of the petal epidermis remain enigmatic. Here, we unveil that the petal surface of Hibiscus trionum, an emerging model system featuring a bullseye on its corolla, is pre-patterned as the position of the bullseye boundary is specified long before the motif becomes visible to the human eye. Using a 1-D computational model, we explore how a boundary established at such an early stage can be maintained throughout development. Reciprocally, by exploiting transgenic lines and natural variants, we show that plants can regulate the relative position of the boundary during the pre-patterning phase or modulate division and growth on either side of this boundary at later developmental stages to yield variations in final bullseye proportions. Finally, we provide evidence that such modifications in bullseye size have functional significance as buff-tailed bumblebees (Bombus terrestris) can reliably identify a food source based on the size of its bullseye. Notably, we found that individuals exhibit a clear preference for the larger bullseye of H. trionum over the smaller pattern of its close relative, H. richardsonii.

plant biology↗

bioRxiv2021

A 3D gene expression atlas of the floral meristem based on spatial reconstruction of single nucleus RNA sequencing data

Identity and functions of plant cells are influenced by their precise cellular location within the plant body. Cellular heterogeneity in growth and differentiation trajectories results in organ patterning. Therefore, assessing this heterogeneity at molecular scale is a major question in developmental biology. Single-cell transcriptomics (scRNA-seq) allows to characterize and quantify gene expression heterogeneity in developing organs at unprecedented resolution. However, the original physical location of the cell is lost during the scRNA-seq procedure. To recover the original location of cells is essential to link gene activity with cellular function and morphology. Here, we reconstruct genome-wide gene expression patterns of individual cells in a floral meristem by combining single-nuclei RNA-seq with 3D spatial reconstruction. By this, gene expression differences among meristematic domains giving rise to different tissue and organ types can be determined. As a proof of principle, the data are used to trace the initiation of vascular identity within the floral meristem. Our work demonstrates the power of spatially reconstructed single cell transcriptome atlases to understand plant morphogenesis. The floral meristem 3D gene expression atlas can be accessed at http://threed-flower-meristem.herokuapp.com

plant biology↗

bioRxiv2020

A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control

The link between gene regulation and morphogenesis of multicellular organisms is a fundamental problem in biology. We address this question in the floral meristem of Arabidopsis, which generates new tissues and organs through complex changes in growth patterns. Starting from high-resolution time-lapse images, we generated a comprehensive 4-D atlas of early flower development including cell lineage, cellular growth rates and the expression patterns of 28 regulatory genes. This information was introduced in MorphoNet, a web-based open-access platform. The application of mechanistic computational models indicated that the molecular network based on the literature only explained a minority of the expression patterns. This was substantially improved by adding single regulatory hypotheses for individual genes. We next used the integrated information to correlate growth with the combinatorial expression of multiple genes. This led us to propose a set of hypotheses for the action of individual genes in morphogenesis, not visible by simply correlating gene expression and growth. This identified the central transcription factor LEAFY as a potential regulator of heterogeneous growth, which was supported by quantifying growth patterns in a leafy mutant. By providing an integrated, multiscale view of flower development, this atlas should represent a fundamental step towards mechanistic multiscale-scale models of flower development.

developmental biology↗

bioRxiv2019

Long read sequencing of 1,817 Icelanders provides insight into the role of structural variants in human disease

Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spanning a median of 10 Mb per haploid genome. We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association with a rare (AF = 0.037%) deletion of the first exon of PCSK9. Carriers of this deletion have 0.93 mmol/L (1.31 SD) lower LDL cholesterol levels than the population average (p-value = 7.0{middle dot}10-20). We also discovered an association with a multi-allelic SV inside a large repeat region, contained within single long reads, in an exon of ACAN. Within this repeat region we found 11 alleles that differ in the number of a 57 bp-motif repeat, and observed a linear relationship (0.016 SD per motif inserted, p = 6.2{middle dot}10-18) between the number of repeats carried and height. These results show that SVs can be accurately characterized at population scale using long read sequence data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.

genetics↗

bioRxiv2019

Genome Sequence of Segmented Filamentous Bacteria Present in the Human Intestine

Segmented filamentous bacteria (SFB) colonize the small intestine of a variety of animals in a host-specific manner. SFB are physically attached to the hosts intestinal epithelium and affect several functions related to the immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome had been described. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with the SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65-71% average amino acid identity to the other genomes, and is tentatively unique for the human small intestine. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB-genome. We thus conclude that a unique SFB variant exists in humans and we foresee a renewed interest in the elucidation of SFB functionality in this environment.

microbiology↗

bioRxiv2019

Cytoskeletal organization in isolated plant cells under geometry control.

Specific cell and tissue form is essential to support many biological functions of living organisms. During development, the creation of different shapes at the cellular and tissue level fundamentally requires the integration of genetic, biochemical and physical inputs.\n\nIt is well established that the cortical microtubule network plays a key role in the morphogenesis of the plant cell wall by guiding the organisation of new cell wall material. Moreover, it has been suggested that light or mechanical stresses can orient the microtubules thereby controlling wall architecture and plant cell shape. The cytoskeleton is thus a major determinant of plant cell shape. What is less clear is how cell shape in turn influences cytoskeletal organization.\n\nRecent in vitro experiments and numerical simulations predicted that a geometry-based rule is sufficient to explain some of the microtubule organization observed in cells. Due to their high flexural rigidity and persistence length of the order of a few millimeters, MTs are rigid over cellular dimensions and are thus expected to align along their long axis if constrained in specific geometries. This hypothesis remains to be tested in cellulo.\n\nHere we present an experimental approach to explore the relative contribution of geometry to the final organization of actin and microtubule cytoskeletons in single plant cells. We show that, in cells constrained in rectangular shapes, the cytoskeleton align along the long axis of the cells. By studying actin and microtubules in cells with the same system we show that while actin organisation requires microtubules to be present to align the converse is not the case. A model of self organizing microtubules in 3D predicts that severing of microtubules is an important parameter controlling the anisotropy of the microtubule network. We experimentally confirmed the model predictions by analysing the response to shape change in plant cells with altered microtubule severing dynamics. This work is a first step towards assessing quantitatively how cell geometry contributes to the control of cytoskeletal organization in living plant cells.

biophysics↗

bioRxiv2019

PopDel identifies medium-size deletions jointly in tens of thousands of genomes

Thousands of genomic structural variants segregate in the human population and can impact phenotypic traits and diseases. Their identification in whole-genome sequence data of large cohorts is a major computational challenge. We describe a novel approach, PopDel, which jointly identifies deletions of about 500 to at least 10,000 bp in length in many genomes together. PopDel scales to tens of thousands of genomes as we demonstrate in evaluations on up to 49,962 genomes. We show that PopDel reliably reports common, rare and de novo deletions. On genomes with available high-confidence reference call sets PopDel shows excellent recall and precision. Genotype inheritance patterns in up to 6,794 trios indicate that genotypes predicted by PopDel are more reliable than those of previous SV callers. Furthermore, PopDels running time is competitive with the fastest tested previous tools. The demonstrated scalability and accuracy of PopDel enables routine scans for deletions in large-scale sequencing studies.

bioinformatics↗

bioRxiv2019

Limits and constraints on mechanisms of cell-cycle regulation imposed by cell size-homeostasis measurements

High-throughput imaging has led to an explosion of observations regarding cell-size homeostasis across the kingdoms of life. Among bacteria, \"adder\" behavior in which a constant size appears to be added during each cell cycle is ubiquitous, while various eukaryotes show other size-homeostasis behaviors. Since interactions between cell-cycle progression and growth ultimately determine size-homeostasis behaviors, we developed a general model of cell proliferation to: 1) discover how the requirement of cell-size homeostasis limits mechanisms of cell-cycle control; 2) predict how features of cell-cycle control translate into size-homeostasis measurements. Our analyses revealed plausible cell-cycle control scenarios that nevertheless fail to regulate cell size, conditions that generate apparent adder behavior without underlying adder mechanisms, cell-cycle features that play unintuitive roles in causing deviations from adder, and distinguishing predictions for extended size-homeostasis statistics according to the underlying control mechanism. The model thus provides holistic insight into the mechanistic implications of cell-size homeostasis measurements.

systems biology↗

bioRxiv2019

DRAFT - Robotic automation of production and the recovery of cell spheroids

Droplet microfluidics enables high throughput cell processing, analysis and screening by miniaturizing the reaction vessels to nano-or pico-liter water-in oil droplets, but like many other microfluidic formats, droplet microfluidics have not been interfaced with or automated by laboratory robotics. Here we demonstrate automation of droplet microfluidics based on an inexpensive liquid handling robot for the automated production of human scaffold-free cell spheroids, using pipette actuation and interfacing the pipetting tip with a droplet generating microfluidic chip. In this chip we produce highly mono-disperse 290m droplets with diameter CV of 1.7%. By encapsulating cells in these droplets we produce cell spheroids in droplets and recover them to standard formats at a throughput of 85000 spheroids per microfluidic circuit per hour. The viability of the cells in spheroids remains high after recovery only decreased by 4% starting from 96% after 16 hours incubation in nanoliter droplets. Scaffold-free cell spheroids and 3D tissue constructs recapitulate many aspects of functional human tissue more accurately than 2D or single cell cultures, but assembly methods for spheroids, e.g. hanging drop micro-plates, has had limited throughput. The increased throughput and decreased cost of our method enables spheroid production at the scale needed for lead discovery drug screening and approaches the cost where these micro tissues could be used as building blocks for organ scale regenerative medicine.

bioengineering↗

bioRxiv2017

Recurrence of de novo mutations in families

De novo mutations (DNMs) cause a large fraction of severe rare diseases of childhood. DNMs that occur in early embryos may result in mosaicism of both somatic and germ cells. Such early mutations may be transmitted to more than one offspring and cause recurrence of serious disease. We scanned 1,007 sibling pairs from 251 families and identified 885 DNMs shared by siblings (ssDNMs) at 451 genomic sites. We estimated the probability of DNM recurrence based on presence in the blood of the parent, sharing by other siblings, parent-of-origin, mutation type, and genomic position. We detected 52.1% of ssDNMs in the parental blood. The probability of a DNM being shared goes down by 2.28% per year for paternal DNMs and 1.82% for maternal DNMs. Shared paternal DNMs are more likely to be T>C mutations than maternal ones, but less likely to be C>T mutations. Depending on DNM properties, the probability of recurrence in a younger sibling ranges from 0.013% to 29.6%. We have launched an online DNM recurrence probability calculator, to use in genetic counselling in cases of rare genetic diseases.

genomics↗

bioRxiv2017

The self-organization of plant microtubules in three dimensions enables stable cortical localization and sensitivity to external cues

Many cell functions rely on the ability of microtubules to self-organize as complex networks. In plants, cortical microtubules are essential to determine cell shape as they guide the deposition of cellulose microfibrils, and thus control mechanical anisotropy in the cell wall. Here we analyze how, in turn, cell shape may influence microtubule behavior. Using a computational model of microtubules enclosed in a three-dimensional space, We show that the microtubule network has spontaneous configurations that could explain many experimental observations without resorting to specific regulation. In particular, we find that the preferred localization of microtubules at the cortex emerges from directional persistence of the microtubules, combined with their growth mode. We identified microtubule parameters that seem relatively insensitive to cell shape, such as length or number. In contrast, microtubule array anisotropy depends strongly on local curvature of the cell surface and global orientation follows robustly the longest axis of the cell. Lastly, we found that the network is capable of reorienting toward weak external directional cues. Altogether our simulations show that the microtubule network is a good transducer of weak external polarity, while at the same time, it easily reaches stable global configurations.\n\nAuthor summaryPlants exhibit an astonishing diversity in architecture and shape. A key to such diversity is the ability of their cells to coordinate and grow to reach a broad spectrum of sizes and shapes. Cell growth in plants is guided by the microtubule cytoskeleton. Here, we seek to understand how microtubules self-organize close to the cell surface. We build upon previous two-dimensional models and we consider microtubules as lines growing in three dimensions, accounting for interactions between microtubules or between microtubules and the cell surface. We show that microtubule arrays are able to adapt to various cell shapes and to reorient in response to factors such as signals or environment. Altogether, our results help to understand how the microtubule cytoskeleton contributes to the diversity of plant shapes and to how these shapes adapt to environment.

cell biology↗