Biology subjects

Sundstrom, E.

Publications and source records attributed to Sundstrom, E..

13 recordsLinked to original sources

bioRxiv2026

Fluidized Bed Cathodes Enable High-Rate CO2 to Formate Production and In Situ Microbial Growth

Electrochemical CO2 Reduction Reaction (eCO2RR) to formate offers a sustainable and promising route for storing renewable electricity in a microbial energy substrate. Conventional CO2 electrolyzers rely on flat electrodes with limited catalytic surface area, mass-transfer constraints, and electrolytes that are incompatible with microbial growth, preventing direct coupling of electrochemical formate production with biological conversion. Here, we developed a biocompatible CO2 electrolysis configuration that uses fluidized particles of Sn, Bi, and In as electrocatalysts to enhance CO2 to formate conversion while supporting microbial utilization in the same chamber. The fluidized configuration enabled high formate production rates up to 0.24 mmol cm2 with Faradaic efficiencies of 86 to 92%, representing a two fold improvement over static electrodes. The system also achieved a carbon conversion efficiency of 42%, approaching the theoretical limit for co-generation of formate and bicarbonate. Importantly, electrolysis was performed in a biocompatible medium that supported direct in situ cultivation of Cupriavidus necator within the cathode chamber using only electricity and CO2/O2 as fed substrates. C. necator continuously consumed electro-generated formate for 5 to 6 days under aerobic conditions, demonstrating integrated CO2 to biomass conversion. This work establishes a fluidized electrocatalytic platform for simultaneous electrosynthesis and microbial upgrading in a single reactor, providing a scalable strategy for renewable carbon fixation and sustainable biomanufacturing.

bioengineering↗

bioRxiv2026

Dog-human gene network colocalization links synaptic signalling and ubiquitination to compulsive disorders

Obsessive-compulsive disorder (OCD) is highly polygenic, and the largest genome-wide association study (GWAS), with 53,660 cases and 2,044,417 controls, identified only 30 loci, a small fraction of loci estimated to explain its heritability - too few to resolve biological pathways. Pet dogs develop a compulsive disorder (dogCD) similar to OCD. In a GWAS of dogCD with 2,584 dogs from the community science project Darwin's Ark, each dog locus explains at least 40-fold more phenotypic variance than each human OCD locus, giving power equivalent to the human GWAS with 80-fold fewer individuals. Combining the two GWAS identifies a 165-gene network undetectable in humans at current sample sizes. This network is enriched for genes expressed in neurons, particularly in the amygdala and cortex, and comprises four biological processes: excitatory-inhibitory synaptic transmission, axon guidance and neuron recognition, protein ubiquitination, and adenylyl cyclase-activating G-protein-coupled receptor signaling. Like most complex human traits, dogCD risk is likely driven by regulatory variation: fine-mapped dogCD SNPs are non-coding, and dogCD loci are enriched in candidate cis-regulatory elements (cCREs) in a new dog epigenomic atlas spanning eight brain regions. The cross-species network implicates an inherited risk architecture largely outside current OCD pharmacotherapy, and establishes pet dogs as a model for gene network discovery, particularly for conditions underpowered in human studies.

genetics↗

bioRxiv2026

A single nuclei expression resource for exploring dog brain cell transcriptomic diversity

Domesticated dogs present a unique case in nature where mutualism with and selective breeding by humans has led to profound changes in their environment, physiology, and behaviour compared to their wolf-like ancestors. Dog tameness, sociability, and trainability have likely evolved due to significant alterations to brain function. Exploring the effects of domestication on the dog brain will be facilitated by the characterisation of dog brain cell diversity, a task which is not yet complete. To fill this gap, we use single-nucleus RNA sequencing and survey cell types across the dog brain. We present transcriptomes from almost 60,000 cells sampled from the cerebellum, thalamus, and three regions of the cerebrum. Our analysis identified 24 major clusters representing 21 broad cell types, and 131 subclusters revealing regional variation. Comparisons with human and mouse datasets revealed a high level of conservation in neurons across mammalian brains, and greater divergence in glial cells, particularly oligodendrocytes. We demonstrate the utility of the dataset for interrogating specific gene expression patterns across the brain, including genes implicated in dog domestication, behavioural traits, and disease. We discover distinct differences in the expression of opioid receptors in the brains of dogs, compared to humans and mice, providing a potential explanation for dogs' higher tolerance and lower risk of severe adverse effects of opioid drugs. The data from this project are released via a web application for use by the wider community.

genomics↗

bioRxiv2025

Cell atlas of the developing human meninges reveals a dura origin of meningioma

The vertebrate central nervous system is enveloped by the meninges, consisting of the pia, arachnoid, and dura layers. The arachnoid is hypothesised to give rise to the most common primary intracranial tumours, meningiomas. However, molecular evidence supporting this hypothesis is lacking. There are no effective medical therapies to treat meningiomas that are resistant to local interventions, encumbered by our limited understanding of their cellular origin. To address this limitation in our understanding of meningioma biology, we generated a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges at post-conceptional weeks 5-13. We found that the meningeal layers develop concurrently, and identified an inner CDH1-positive dura cell layer expressing tight junction genes consistent with barrier function. We show that transcriptionally, meningioma cells resemble dura-lineage cells, and that common meningioma driver genes were expressed preferentially in the dura lineage. Our findings suggest that meningiomas originate from dura lineage cells. HIGHLIGHTSO_LIscRNA-seq and spatial transcriptomics reveals architecture of human fetal meninges development C_LIO_LIMeningeal layers are formed concurrently, by a gradual refinement of cell states C_LIO_LIA CDH1+ inner dura sublayer expresses tight junction genes like the arachnoid barrier C_LIO_LIMeningioma tumours likely originate from inner dura lineage cells, not arachnoid C_LI

developmental biology↗

bioRxiv2024

Spatial Dynamics of the Developing Human Heart

Heart development relies on a topologically defined interplay between a diverse array of cardiac cells. We finely curated spatial and single-cell measurements with subcellular imaging-based transcriptomics validation to explore spatial dynamics during early human cardiogenesis. Analyzing almost 80,000 individual cells and 70,000 spatially barcoded tissue regions between the 5.5th and 14th postconceptional weeks, we identified 31 coarse- and 72 fine-grained cell states and mapped them to highly resolved cardiac cellular niches. We provide novel insight into the development of the cardiac pacemaker-conduction system, heart valves, and atrial septum, and decipher heterogeneity of the hitherto elusive cardiac fibroblast population. Furthermore, we describe the formation of cardiac autonomic innervation and present the first spatial account of chromaffin cells in the fetal human heart. We support independent exploration of our datasets by an open-access, spatially centric interactive viewer. In summary, our study delineates the cellular and molecular landscape of the developing hearts architecture, offering links to genetic causes of heart disease.

developmental biology↗

bioRxiv2024

High-parametric protein maps reveal the spatial organization in early-developing human lung

The respiratory system, including the lungs, is essential for terrestrial life. While recent research has advanced our understanding of lung development, much still relies on animal models and transcriptome analyses. In this study conducted within the Human Developmental Cell Atlas (HDCA) initiative, we describe the protein-level spatiotemporal organization of the lung during the first trimester of human gestation. Using high-parametric tissue imaging with a 30-plex antibody panel, we analyzed human lung samples from 6 to 13 post-conception weeks, generating data from over 2 million cells across five developmental timepoints. We present a resource detailing spatially resolved cell type composition of the developing human lung, including proliferative states, immune cell patterns, spatial arrangement traits, and their temporal evolution. This represents an extensive single-cell resolved protein-level examination of the developing human lungs and provides a valuable resource for further research into the developmental roots of human respiratory health and disease.

developmental biology↗

bioRxiv2023

Dynamics of chromatin accessibility during human first-trimester neurodevelopment

The human brain is capable of highly complex functions that develops through a tightly organized cascade of patterning events, expressed transcription factors and changes in chromatin accessibility. While extensive datasets exist describing gene expression across the developing brain with single-cell resolution, similar atlases of chromatin accessibility have been primarily focused on the forebrain. Here, we focus on the chromatin landscape and paired gene expression across the developing human brain to provide a comprehensive single cell atlas during the first trimester (6 - 13 post-conceptional weeks). We identified 135 clusters across half a million nuclei and using the multiomic measurements linked candidate cis-regulatory elements (cCREs) to gene expression. We found an increase in the number of accessible regions driven both by age and neuronal differentiation. Using a convolutional neural network we identified putative functional TF-binding sites in enhancers characterizing neuronal subtypes and we applied this model to cCREs upstream of ESRRB to elucidate its activation mechanism. Finally, by linking disease-associated SNPs to cCREs we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being the most vulnerable to major depressive disorder related mutations. Together, our findings provide a higher degree of detail to some key gene regulatory mechanisms underlying the emergence of cell types during the first trimester. We anticipate this resource to be a valuable reference for future studies related to human neurodevelopment, such as identifying cell type specific enhancers that can be used for highly specific targeting in in vitro models.

developmental biology↗

bioRxiv2022

Decoding spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin

The human spinal cord contains diverse cell types, governed by a series of spatiotemporal events for tissue assembly and functions. However, the spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. Single-cell RNA sequencing and spatial transcriptomics techniques have advanced the understanding of human organ development considerably. By performing integrated analysis of single-cell and spatial multi-omics methods, we created a comprehensive developmental cell atlas of the first trimester human spinal cord. Our data revealed that the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. Beyond this resource, we unexpectedly discovered unique events in human spinal cord development compared to rodents, including earlier quiescence of active neural stem cells, different regulation of stem cell differentiation, and distinct spatiotemporal genetic regulations of cell fate choices. In addition, using our atlas we identified specific gene expression in cancer stem cells in ependymomas. Thus, we demonstrate spatiotemporal genetic regulation of human spinal cord development as well as its potential to understand novel disease mechanisms and to inspire new therapies.

developmental biology↗

bioRxiv2021

Developmental landscape of human forebrain at a single-cell level unveils early waves of oligodendrogenesis

Oligodendrogenesis in the human central nervous system has been mainly observed at the second trimester of gestation, a much later developmental stage compared to mouse. Here we characterize the transcriptomic neural diversity in the human forebrain at post conceptual weeks (PCW) 8 to 10, using single-cell RNA-Seq. We find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level with single-cell ATAC-Seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of fifty key genes using In Situ Sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mouse and human and describe regulatory mechanisms required for human OPC specification.

neuroscience↗

bioRxiv2020

Heterochiasmy facilitated the establishment of gsdf as a novel sex determining gene in Atlantic halibut

Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male- and female restricted meiotic recombination intervals (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. We propose that heterochiasmy may facilitate the evolution of genetic sex determination systems.

genomics↗

bioRxiv2020

A new long-read dog assembly uncovers thousands of exons and functional elements missing in the previous reference

Here we present a new high-quality canine reference genome with gap number reduced 41-fold, from 23,836 to 585. Analysis of existing and novel data, RNA-seq, miRNA-seq and ATAC-seq, revealed a large proportion of these harboured previously hidden elements, including genes, promoters and miRNAs. Short-read dark regions were detected, and genomic regions completed, including the DLA, TCR and 366 cancer genes. 10x sequencing of 27 dogs uncovered a total of 22.1 million SNPs, Indels and larger structural variants (SVs). 1.4% overlap with protein coding genes and could provide a source of normal or aberrant phenotypic modifications.

genomics↗

bioRxiv2017

RNA velocity in single cells

RNA abundance is a powerful indicator of the state of individual cells, but does not directly reveal dynamic processes such as cellular differentiation. Here we show that RNA velocity--the time derivative of RNA abundance--can be estimated by distinguishing unspliced and spliced mRNAs in standard single-cell RNA sequencing protocols. We show that RNA velocity is a vector that predicts the future state of individual cells on a timescale of hours. We validate the accuracy of RNA velocity in the neural crest lineage, demonstrate its use on multiple technical platforms, reconstruct the branching lineage tree of the mouse hippocampus, and measure RNA kinetics in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.

genomics↗

bioRxiv2017

Rhodosporidium toruloides: A new platform organism for conversion of lignocellulose into terpene biofuels and bioproducts

BackgroundEconomical conversion of lignocellulosic biomass into biofuels and bioproducts is central to the establishment of a robust bioeconomy. This requires a conversion host that is able to both efficiently assimilate the major lignocellulose-derived carbon sources and divert their metabolites toward specific bioproducts.\n\nResultsIn this study, the carotenogenic yeast Rhodosporidium toruloides was examined for its ability to convert lignocellulose into two non-native sesquiterpenes with biofuel (bisabolene) and pharmaceutical (amorphadiene) applications. We found that R. toruloides can efficiently convert a mixture of glucose and xylose from hydrolyzed lignocellulose into these bioproducts, and unlike many conventional production hosts, its growth and productivity were enhanced in lignocellulosic hydrolysates relative to purified substrates. This organism was demonstrated to have superior growth in corn stover hydrolysates prepared by two different pretreatment methods, one using a novel biocompatible ionic liquid (IL) choline -ketoglutarate, which produced 261 mg/L of bisabolene at bench-scale, and the other using an alkaline pretreatment, which produced 680 mg/L of bisabolene in a high gravity fed-batch bioreactor. Interestingly, R. toruloides was also observed to assimilate p-coumaric acid liberated from acylated grass lignin in the IL hydrolysate, a finding we verified with purified substrates. R. toruloides was also able to consume several additional compounds with aromatic motifs similar to lignin monomers, suggesting that this organism may have the metabolic potential to convert depolymerized lignin streams alongside lignocellulosic sugars.\n\nConclusionsThis study highlights the natural compatibility of R. toruloides with bioprocess conditions relevant to lignocellulosic biorefineries and demonstrates its ability to produce non-native terpenes.

bioengineering↗