Biology subjects

Svenningsson, P.

Publications and source records attributed to Svenningsson, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Spatial organization and mitigation of autofluorescence in multiplexed spatial proteomics of aged fresh-frozen human brain

Multiplexed imaging technologies are transforming the study of human tissue biology, but their application to the aged brain is hindered by autofluorescence, particularly in fresh-frozen specimens. Here, we characterized autofluorescence across four brain regions from 21 donors and found broad spectral emission, regional and gray-white matter differences, and an association with donor age. Photobleaching conditions adopted from formalin-fixed paraffin-embedded tissue caused marked region- and compartment-dependent damage in fresh-frozen sections. We therefore developed a Tris-EDTA-supplemented photobleaching workflow that reduced autofluorescence by 58-70% while preserving tissue architecture and cellular content. We established a custom 28-plex DNA-barcoded antibody panel targeting neuronal, glial, immune, and vascular markers, providing a resource for fresh-frozen human brain. Integration of the optimized photobleaching workflow with this panel enabled spatial proteomic analysis across fresh-frozen brain regions. By co-registering pre-photobleaching autofluorescence with multiplexed protein maps, we further established a cellular-resolution framework for spatial characterization of autofluorescence. This revealed region-dependent protein marker relationships and preferential enrichment of autofluorescent particles near nuclei and within microglial and CD68-positive regions. Together, this work establishes a practical workflow for multiplexed spatial proteomics in fresh-frozen brain and characterizes autofluorescence as both a technical confound and a spatially structured feature of the aged human brain.

neuroscience↗

bioRxiv2026

Advancing Neurological Liquid Biopsy via Six-Base Sequencing of Cerebrospinal Fluid Cell-Free DNA

Real-time molecular insights into the human brain are crucial for understanding neurological conditions and development of soluble biomarkers but challenged by the limited access to target tissue. Here we utilize 6-base sequencing to profile DNA modifications of cell-free DNA released from neural cells into cerebrospinal fluid. This strategy provides molecular, quantitative and qualitative insights into the ongoing neurodegenerative biology, which paves the way for liquid biopsy approaches to study neurological conditions.

neuroscience↗

bioRxiv2026

Anisotropic conductivity modeling for tDCS in Parkinson's disease using multidimensional diffusion MRI

Transcranial direct current stimulation (tDCS) dose depends on how brain conductivity is modeled. White matter anisotropy is conventionally estimated from single-shell diffusion tensor imaging (DTI). Multidimensional diffusion MRI (MD-dMRI), specifically q-space trajectory imaging (QTI), instead gives a mean tensor expected to carry less kurtosis bias. Our primary question was whether replacing the conventional single-shell tensor with this mean tensor would change the predicted field. We built, to our knowledge, the first MD-dMRI tDCS conductivity model and compared it against DTI and isotropic models in 29 participants (12 with Parkinsons disease, 17 controls) across four montages, with the same mesh, electrodes, and solver. The three models agreed within a few percent. The two anisotropic models differed mainly in tensor orientation (about 21 degrees in white matter), with small differences in field magnitude. Field did not differ between patients and controls in any region or montage (which was an exploratory, underpowered comparison). Whole-brain electric field correlated with MR elastography stiffness (partial r = +0.58) but attenuated to non-significance once cerebrospinal fluid morphology was accounted for (r = +0.06 to +0.09). With no ground-truth field or conductivity available, the study establishes the feasibility of the MD-dMRI model and characterizes field sensitivity rather than improved dosimetry accuracy. The choice of diffusion tensor is second order for dose, which is primarily influenced by individual anatomy. For Parkinsons disease, modeling efforts should focus on cerebrospinal fluid- and atrophy-aware head models and dose normalization, rather than a more complex diffusion tensor. HighlightsO_LIIndividual anatomy, more than the conductivity tensor, governs tDCS dose. C_LIO_LIA first tDCS head model from multidimensional diffusion MRI (QTI). C_LIO_LIMD-dMRI, single-shell DTI and isotropic fields agreed within a few percent. C_LIO_LIThe anisotropic models differ mainly in orientation; their fields agree closely. C_LI

neuroscience↗

bioRxiv2026

In silico evaluation of the effects of temperature on the affinity of the SV2C ligand UCB-1A to SV2 isoforms

Synaptic vesicle glycoproteins 2 (SV2) are integral membrane proteins essential for neurotransmitter release and are implicated in neurological disorders including epilepsy and Parkinsons disease. In the attempt to develop a ligand selective for SV2C, and in collaboration with UCB, UCB-F was identified as a potential candidate. However, the affinity of UCB-F to SV2C was found to be temperature dependent, decreasing by about 10-fold from +4 to 37 degrees. UCB1A was subsequently identified as SV2C ligand displaying in vitro a 100-fold selectivity for SV2C compared with SV2A. In this study we investigated whether the binding of UCB-1A to SV2A and SV2C was affected by the temperature. A combination of experimental binding assay data and molecular dynamics (MD) simulations were used. The binding studies revealed that UCB1A affinity for SV2A decreased significantly at 37 {degrees}C compared with 4 {degrees}C, whereas binding to SV2C remained largely unchanged. MD simulations reproduced these observations, namely that ligand RMSD values at 310 K showed that UCB1A binding fluctuated markedly in the SV2A complex, with many trajectories exceeding the 3.0 [A] stability cutoff, whereas UCB1A remained relatively well-anchored in SV2C under the same conditions. Structural analysis showed that, while UCB1A adopts a conserved binding pose across all isoforms stabilized by {pi}- {pi} stacking and a hydrogen bond with Asp, SV2C possesses a unique stabilizing feature. In SV2C, Tyr298 is less exposed to the solvent and engages in a persistent hydrogen bond with Asparagine, a structural feature that reinforces pocket stability and limits temperature-induced destabilization. This interaction is absent in SV2A, consistent with its greater temperature sensitivity. Together, these findings provide a mechanistic explanation for the experimentally observed temperature independence of UCB1A binding to SV2C. More broadly, the results highlight the importance of incorporating physiologically relevant temperatures into SV2 ligand evaluation and demonstrate how combining experiments with simulations can uncover isoform-specific mechanisms of ligand recognition and stability.

biochemistry↗

bioRxiv2026

Discovery and characterization of UCB-1A: the first PET radioligand for imaging synaptic vesicle glycoprotein 2C

The synaptic vesicle glycoprotein 2C (SV2C) is a synaptic protein involved in the regulation of dopamine release. It is expressed in striatum, globus pallidus and substantia nigra, regions involved in the regulation of motor function. Genome-wide association studies, animal model and human brain tissue data indicate a strong link between SV2C and Parkinso[n]s disease, suggesting a potential role of SV2C as synaptic marker for Parkinso[n]s disease. We hypothesize that a positron emission tomography (PET) radioligand for SV2C can serve as imaging marker for Parkinso[n]s disease, enabling early diagnosis and assessment of disease progression. This study was therefore designed to develop a PET radioligand for imaging SV2C. UCB-1A was the lead candidate selected from a library of compounds developed by UCB BioPharma. A translational approach was used, including autoradiography and in vitro binding studies with [3H]UCB-1A, and in vivo PET studies with [11C]UCB-1A in non-human primates (NHPs). The KD of [3H]UCB-1A for rat and human SV2C ranged between 6 and 15 nM, with >100-fold selectivity towards SV2A and SV2B. Specific binding of [3H]UCB-1A in rat and NHP brains was observed in substantia nigra, globus pallidus, striatum and brainstem nuclei, consistent with the expression of SV2C, and was decreased in the striatum of 6-hydroxydopamine-lesioned rats and in the putamen of Parkinson donors. UCB-1A was successfully radiolabelled with 11C and PET studies in NHPs demonstrated that [11C]UCB-1A displays suitable pharmacokinetic properties, a brain distribution consistent with the expression of SV2C and is selective for SV2C. [11C]UCB-1A is the first PET radioligand for in vivo imaging of SV2C and a potential synaptic marker for in vivo studies in Parkinso[n]s disease.

neuroscience↗

bioRxiv2026

Targeted DNA methylation editing in vivo

The number of epigenome-wide association studies linking CpG DNA methylation with disease, traits and exposures, continues to rise. Despite the rapid development of epigenome editing tools, establishing causation remains challenging, particularly in vivo. In this study, we developed and characterized three Cre-dependent CRISPR-based mouse lines that enable locus-specific DNA methylation deposition by either constitutive or inducible dCas9-DNMT3A expression. We demonstrate robust highly locus-specific DNA methylation deposition at MHC class II (H2-Ab1) and interleukin 6 (Il6) genes in bone marrow-derived myeloid cells ex vivo. Moreover, neuron-specific methylation targeting resulted in reduced cannabinoid receptor 1 (Cnr1) expression in striatal neurons in vivo. Notably, we demonstrate that the causal effect of DNA methylation on gene expression is locus-dependent, reinforcing the necessity of such editing tools for detailed understanding of the role of DNA methylation and for addressing the causality of disease-associated CpGs.

molecular biology↗

bioRxiv2026

Reactive Astrocytes Drive Extracellular Acidification to Mediate α-Synuclein Neurodegeneration

Astrocytes are increasingly recognized as key players in neurodegeneration1-3, yet the molecular mechanisms by which they drive disease remain elusive. Here, we uncover a fundamental pathway in which reactive astrocytes fuel neurodegeneration in -synucleinopathies--including Dementia with Lewy bodies and Parkinsons disease dementia--by acidifying the brains extracellular environment. We demonstrate that both human patient tissue and a gut-to-brain -synuclein mouse model exhibit accumulation of reactive astrocytes and extracellular acidosis. Mechanistically, we show that astrocytic lysosomal exocytosis releases acidic contents, driving a drop in pH that activates neuronal acid-sensing ion channel 1a (ASIC1a), resulting in neuronal loss and behavioral decline. Blocking this pathway--either by inhibiting astrocytic lysosomal exocytosis or genetically or pharmacologically targeting neuronal ASIC1a--mitigates pathology and rescues neurodegenerative phenotypes in vivo. These findings provide a conceptual advance by establishing a mechanistic link between glial inflammation, acid-base homeostasis, and neuronal vulnerability, and suggest that targeting astrocyte-driven acidification or ASIC1a signaling could offer new avenues for disease modification in -synucleinopathies.

neuroscience↗

bioRxiv2025

Development of a protocol utilizing single-cell analysis for the differentiation of human iPSCs into SOX6+ midbrain dopaminergic neurons.

Parkinsons disease (PD) is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons, leading to severe debilitating motor impairment. Recent single-cell analyses have revealed that specific mDA subpopulations, such as SOX6 AGTR1 neurons, are most vulnerable to degeneration. Current human pluripotent stem cell differentiation protocols fail to selectively generate these subtypes. Here, we describe a multiomic-guided strategy that enriches SOX6+ mDA neurons by combining enhancing Sonic Hedgehog agonism with prolonged Wnt activation. This approach accelerates floor plate specification, increases expression of mDA developmental markers, and substantially increases the yield of SOX6 mature mDA neurons compared to prior attempts. Following intrastriatal transplantation into hemiparkinsonian mice, these cells restored motor function in approximately 4 months and generated grafts containing SOX6 A9-like neurons. Our work thus establishes a reproducible differentiation platform for generating the PD-susceptible mDA subtype, providing a foundation for precision disease modelling and subtype-targeted cell replacement therapies.

cell biology↗

bioRxiv2025

Revealing molecular determinants of ligand efficacy and affinity at the D2 dopamine receptor through molecular dynamics simulations

G protein-coupled receptors (GPCRs) control numerous physiological processes and are important therapeutic targets. Despite major research efforts, rational design of drugs that stimulate GPCR signaling is challenging because the molecular basis of activation remains poorly understood. Here, a combination of molecular dynamics simulations and pharmacological assays was used to study the activation mechanism of the D2 dopamine receptor (D2R), a major drug target for central nervous system diseases. Enhanced sampling simulations were performed to identify the key conformational changes involved in D2R activation by dopamine, and a computational platform for ligand profiling based on free energy calculations was developed. Simulations and experimental characterization of a series of dopamine derivatives showed that free energy calculations can predict the effect of small chemical modifications on ligand affinity and efficacy. Furthermore, simulations of D2 dopamine and {beta}2 adrenergic receptor activation revealed that ligand-induced activation of these GPCRs is driven by different molecular mechanisms despite recognizing chemically similar catecholamine agonists. Whereas dopamine interactions with the sixth transmembrane helix primarily drive activation of the D2R, hydrogen bonding with the fifth helix is the key interaction for activation of the {beta}2 adrenergic receptor. Our results highlight the complexity of GPCR activation and illustrate how molecular simulations can provide mechanistic insight and quantitative predictions of ligand activity, enabling structure-based drug design. Significance statementG protein-coupled receptors (GPCRs) on the cell surface recognize ligands such as hormones and neurotransmitters. The binding of the ligand to the receptor leads to the activation of intracellular signaling pathways, a communication system that controls essential physiological functions. GPCRs are therefore important therapeutic targets, and many drugs exert effects by modulating their activity. Here, we use molecular simulations to study the activation mechanism of a dopamine receptor, which is implicated in neurodegenerative and neuropsychiatric disorders. We elucidate the mechanism of receptor activation and develop strategies to predict ligand affinity and efficacy. We also identify differsences in the activation mechanisms of dopamine and adrenergic receptors. These findings provide novel insights into receptor activation and can accelerate the drug discovery process.

biophysics↗

bioRxiv2025

Computational design of constitutively active mutants of Dopamine D2 receptor inspired by ligand-independent activation mechanisms

G protein-coupled receptors (GPCRs) can signal in the absence of agonists through constitutive activity. This activity can be enhanced by mutations, resulting in receptors known as constitutively active mutants (CAMs). Such receptors can be implicated in various physiological and pathophysiological conditions, and also offer significant therapeutic potential. However, the molecular basis of their constitutive activity remains unknown. To investigate how CAMs affect receptor activation, we employed enhanced sampling simulations to study the dopamine D2 receptor (D2R), a key target in central nervous system therapies. Free energy landscape analyses revealed that CAMs promote a conformational shift favoring an active state similar to the agonist-bound receptor. To then identify novel CAMs, we developed a comprehensive strategy combining structural comparison, in-silico residue scanning, and free energy calculations, validated by luminescence-complementation-based assays. Applied to D2R, this approach uncovered a new single-point CAM, D2R-I481.46W, which was functionally validated. Further investigation revealed that this mutation activates allosteric communication pathways primarily involving transmembrane helix 5, particularly Ser1945.43, underscoring its role in transmitting activation signals to the intracellular domain. These findings deepen our understanding of constitutive GPCR activity and demonstrate the utility of this framework for identifying CAMs as ligand-independent models for structural, cellular, and physiological studies.

biophysics↗

bioRxiv2025

Synaptotoxic forms of amyloid-b and a-synuclein act through a common pathway.

It has been suggested that -synuclein (Syn), a major player in Parkinsons disease (PD), plays a role in Alzheimers disease (AD). Several reports have also concluded that Syn and amyloid-{beta} (A{beta}) are mechanistically linked, although how is unclear. Synapse loss is an early feature in both PD and AD and held to be the driver of both diseases. We have previously uncovered a signalling pathway required for A{beta}-driven dendritic spine loss - a non-canonical branch of Wnt signalling known as the Wnt/Planar Cell Polarity (Wnt/PCP) pathway. We asked if a synaptotoxic form of Syn known to impact dendritic spines, the A53T autosomal dominant PD mutant form of Syn (A53T-Syn), might act on synapses through the same pathway. Here, by blocking all Wnt activity with the porcupine inhibitor IWP2, we show that A53T-Syn-driven spine loss is Wnt-dependent. By silencing Daam1, which is unique to Wnt/PCP, we show that A53T-Syn spine loss is Daam1-dependent. Finally, using the pan-ROCK inhibitor fasudil indicates the mechanism also involves ROCK1/2, which Daam1 signals to via RhoA to modulate actin cytoskeletal dynamics within dendritic spines. Together, these observations indicate that A53T-Syn-driven spine loss involves the Wnt/PCP pathway, the same pathway that mediates A{beta} synaptotoxicity. This indicates that A{beta} and Syn are mechanistically connected and that a common pathway is responsible for synapse loss in AD and PD. It also begins to explain why this group of neurodegenerative diseases have many features in common and suggests that drugs which target Wnt/PCP could be of benefit for both AD and PD.

neuroscience↗

bioRxiv2025

Met-ID: An Open-Source Software for Comprehensive Annotation of Multiple On-Tissue Chemical Modifications in MALDI-MSI

Here, we introduce Met-ID, a graphical interface software designed to efficiently identify metabolites from MALDI-MSI datasets. Met-ID enables annotation of m/z features from any type of MALDI-MSI experiment, involving either derivatizing or conventional matrices. It utilizes structural information for derivatizing matrices to generate a subset of targets that contain only functional groups specific to the derivatization agent. The software is able to identify multiple derivatization sites on the same molecule, facilitating identification of the derivatized compound. This ability is exemplified by FMP-10, a reactive matrix that assists the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups. Met-ID also permits users to recalibrate data with known m/z ratios, boosting confidence in mass match results. Furthermore, Met-ID includes a database featuring MS2 spectra of numerous chemical standards, consisting of neurotransmitters and metabolites derivatized with FMP-10, alongside peaks for FMP-10 itself, all accessible directly through the software. The MS2 spectral database supports user-uploaded spectra and enables comparison of these spectra with user-provided tissue MS2 spectra for similarity assessment. Although initially installed with basic data, Met-ID is designed to be customizable, encouraging users to tailor the software to their specific needs. While several MSI-oriented software solutions exist, Met-ID stands out as a pioneer in seamlessly combining both MS1 and MS2 functionalities. Developed in alignment with the FAIR Guiding Principles for scientific software, Met-ID is freely available as an open-source tool on GitHub, ensuring wide accessibility and collaboration.

bioinformatics↗

bioRxiv2024

The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.

The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations in the CHCHD2 and CHCHD10 genes have been linked to severe disorders, including Parkinsons disease and amyotrophic lateral sclerosis. In cultured cells, a small fraction of CHCHD2 and CHCHD10 oligomerize to form a high molecular weight complex of unknown function. Here, we generated a whole-body Chchd2 knockout mouse to investigate the in vivo role of CHCHD2 and its protein complex. We show that CHCHD2 is crucial for sustaining full motor capacity, normal striatal dopamine levels, and lipid homeostasis in the brain of adult male mice. We also demonstrate that in mouse tissues, CHCHD2 and CHCHD10 exist exclusively as a high molecular weight complex, whose levels are finely tuned under physiological conditions. In response to mitochondrial dysfunction, the abundance and size of the CHCHD2-CHCHD10 complex increases, a mechanism conserved across different tissues. Although the loss of CHCHD2 does not abolish CHCHD10 oligomerization, it enhances cell vulnerability to mitochondrial stress, suggesting that CHCHD2 is protective against mitochondrial damage. Our findings uncover the role of CHCHD2 in preserving tissue homeostasis and provide important insights into the involvement of the CHCHD2-CHCHD10 complex in human diseases.

neuroscience↗

bioRxiv2024

Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder

Parkinsons disease (PD) is characterized by progressive motor as well as less recognized non-motor symptoms that arise often years before motor manifestation, including sleep and gastrointestinal disturbances. Despite the heavy burden on the patients quality of life, these non-motor manifestations are poorly understood. To elucidate the temporal dynamics of the disease, we employed a mouse model involving injection of alpha-synuclein (Syn) pre-formed fibrils (PFF) in the duodenum and antrum as a gut-brain model of Parkinsonism. Using anatomical mapping of Syn-PFF propagation and behavioral and physiological characterizations, we unveil a correlation between post-injection time the temporal dynamics of Syn propagation and non-motor/motor manifestations of the disease. We highlight the concurrent presence of Syn aggregates in key brain regions, expressing acetylcholine or dopamine, involved in sleep duration, wakefulness, and particularly REM-associated atonia corresponding to REM behavioral disorder-like symptoms. This study presents a novel and in-depth exploration into the multifaceted nature of PD, unraveling the complex connections between -synucleinopathies, gut-brain connectivity, and the emergence of non-motor phenotypes. One Sentence SummaryPropagation of Syn from the gut-to-the-brain induces RBD and several non-motor and motor phenotypes of Parkinsons disease.

neuroscience↗

bioRxiv2023

Expanding the GPCR-RAMP interactome

Receptor activity-modifying proteins (RAMPs) can form complexes with G protein-coupled receptors (GPCRs) and regulate their cellular trafficking and pharmacology. RAMP interactions have been identified for about 50 GPCRs, but only a few GPCR-RAMP complexes have been studied in detail. To elucidate a complete interactome between GPCRs and the three RAMPs, we developed a customized library of 215 Dual Epitope-Tagged (DuET) GPCRs representing all GPCR subfamilies. Using a multiplexed suspension bead array (SBA) assay, we identified 122 GPCRs that showed strong evidence for interaction with at least one RAMP. We screened for native interactions in three cell lines and found 23 GPCRs that formed complexes with RAMPs. Mapping the GPCR-RAMP interactome expands the current system-wide functional characterization of RAMP-interacting GPCRs to inform the design of selective GPCR-targeted therapeutics. One-Sentence SummaryNovel complexes between G protein-coupled receptors and interacting proteins point to a system-wide regulation of GPCR function.

biochemistry↗

bioRxiv2023

Parkin is not required to sustain OXPHOS function in adult mammalian tissues

Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinsons disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of Parkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous PRKN pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.

cell biology↗

bioRxiv2023

Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model

Midbrain dopamine (mDA) neurons comprise diverse cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA neurons of the substantia nigra compacta (SNc) in patients with Parkinsons disease, while those in the ventral tegmental area (VTA) are relatively spared. Here we used single nuclei RNA sequencing (snRNA-seq) of approximately 70,000 mouse midbrain cells to build a high-resolution atlas of mouse mDA neuron diversity at the molecular level. The results showed that differences between mDA neuron groups could best be understood as a continuum without sharp differences between subtypes. Thus, we assigned mDA neurons to several "territories" and "neighborhoods" within a shifting gene expression landscape where boundaries are gradual rather than discrete. Based on the enriched gene expression patterns of these territories and neighborhoods, we were able to localize them in the adult mouse midbrain. Moreover, because the underlying mechanisms for the variable sensitivities of diverse mDA neurons to pathological insults are not well understood, we analyzed surviving neurons after partial 6-hydroxydopamine (6-OHDA) lesions to unravel gene expression patterns that correlate with mDA neuron vulnerability and resilience. Together, this atlas provides a basis for further studies on the neurophysiological role of mDA neurons in health and disease.

neuroscience↗

bioRxiv2023

Spatial Multimodal Analysis of Transcriptomes and Metabolomes in Tissues

We present a spatial omics approach that merges and expands the capabilities of independently performed in situ assays on a single tissue section. Our spatial multimodal analysis combines histology, mass spectrometry imaging, and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular weight metabolites across tissue regions. We demonstrate the potential of our method using murine and human brain samples in the context of dopamine and Parkinsons disease.

genomics↗