Biology subjects

Simard, S.

Publications and source records attributed to Simard, S..

7 recordsLinked to original sources

bioRxiv2026

SCORPy: Lowering the computational barrier to reproducible multiplexed imaging spatial single cell proteomics analysis

Spatially resolved single-cell proteomic imaging technologies, including cyclic immunofluorescence (CycIF), generate high-dimensional data, critical for tissue-scale biological analysis. However, single-cell analysis remains computationally demanding, lacks standardization across platforms and is often inaccessible to experimental biologists without programming expertise. Here we present SCORPy (Single-Cell proteOmics Research Platform), a standalone, cross-platform desktop application that provides an end-to-end, code-free workflow for the analysis of single-cell proteomic data extracted from imaging experiments. SCORPy introduces methodological advances for preprocessing multiplexed imaging data: an exposure-aware, cycle-matched background correction strategy, and a normalization framework that harmonizes signal distributions across markers while enabling batch correction across experiments. These approaches are integrated with quality control, interactive thresholding and cell phenotyping using a hierarchical cell reference library, and downstream compositional and spatial analyses within a unified interface. Sample-level metadata can be incorporated throughout the workflow to support integrative analyses and facilitate generation of publication-ready visualizations. By combining robust preprocessing methods with an accessible implementation, SCORPy reduces computational barriers and promotes broader adoption of spatial single-cell proteomics analysis.

cell biology↗

bioRxiv2025

Bmal1 expression is minimal or absent in human and mouse cerebral microglia

Microglia orchestrate immunological responses in the brain and play an important role in maintaining homeostatic brain functions. Several studies have reported clock gene expression in microglia and the circadian rhythm they drive has been linked to the modulation of immune responses and neuronal functions. In the current study, complementary approaches, including immunofluorescence, multiplexed fluorescence in situ hybridization, and liquid chromatography-mass spectrometry proteomics of isolated CD11b+ microglia, were combined with publicly available transcriptomic and epigenomic datasets to investigate the expression of the core clock gene BMAL1 in human post-mortem cortical and limbic areas as well as mouse brain. The majority of BMAL1-expressing cells were found to be neurons, with microglia representing a negligeable proportion. We also identified significantly lower chromatin accessibility or "openness" for BMAL1 gene regulatory regions (such as promoters and enhancers) in microglia compared to neurons. These regulatory regions in microglia were enriched for ETS domain transcription factor (TF) binding sites. Together, this suggests a strong role of chromatin remodeling factors in suppressing BMAL1 gene expression in microglia. Finally, while we observed a very low expression, BMAL1 TF motifs were accessible in open chromatin landscape of microglia, which may lead to downstream gene-regulatory effects upon binding, even if BMAL1 expression is constitutively low. Overall, our results reveal low or absent expression of BMAL1 in microglia and point towards potential epigenetic mechanisms regulating its expression in these cells.

neuroscience↗

bioRxiv2025

Optogenetic stimulation of nigral astrocytes is neuroprotective in a 6-OHDA model of neurodegeneration.

HighlightsO_LIOptogenetic stimulation of nigral astrocytes attenuates motor deficits & Th+ cell loss in a 6-OHDA model of neurodegeneration C_LIO_LIBulk RNA-seq analysis reveals optogenetic stimulation of nigral astrocytes induces early changes in microglia C_LIO_LIsnRNA-seq shows 6-OHDA alone induces extensive gene expression changes across all cell populations within the SN C_LIO_LIOligodendrocytes within the SNc express Th, which is upregulated with DA neuron loss C_LI Parkinsons disease is characterized by the loss of dopaminergic neurons in the substantia nigra. Glial-glial crosstalk is essential for maintaining the regional milieu, and appears to be particularly important in modulating neuroinflammation and many aspects of neurodegeneration. In particular, astrocytes are critical for maintaining dopamine neuronal integrity and survival, and astroglial dysfunction is prominent in Parkinsons disease. As such, astrocytes represent a potentially critical therapeutic target in neurodegeneration. In this study, in vivo optogenetics were used to selectively stimulate astrocytes in the substantia nigra following a striatal 6-OHDA lesion. Remarkably, a single bout of optogenetic stimulation was sufficient to attenuate motor deficits and dopamine neuron loss induced by the neurotoxin. Furthermore, bulk RNA-seq and snRNA-seq analysis of the substantia nigra revealed extensive changes in both microglia and oligodendrocytes, suggesting that the neuroprotective effects of stimulating astrocytes may be mediated through alterations in glia-glia crosstalk. Altogether, this work demonstrates the importance of understanding glia-glia interactions in neurodegeneration.

neuroscience↗

bioRxiv2023

Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain

Using spatial transcriptomics and FISH, we detected very few cells expressing neural stem cell- and proliferation-specific genes in the human dentate gyrus (DG) from childhood to middle age. However, we observed at all ages a significant number of DG cells expressing the immature neuronal marker DCX. Across ages, the majority of these cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.

neuroscience↗

bioRxiv2022

Early-life stress lastingly impacts microglial transcriptome and function under basal and immune-challenged conditions

Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (postnatal days [P]2 - 9) on microglial i) morphology; ii) hippocampal gene expression; and iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to CTRL microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.

neuroscience↗

bioRxiv2019

Translatomic database of cortical astroglia across male and female mouse development reveals two distinct developmental phenotypes

Astroglial cells are emerging as key players in the development and homeostatic maintenance of neurons and neuronal networks. Astroglial cell functions are critical to neuronal migration and maturation, myelination, and synapse dynamics, however little is known about astroglial phenotypic changes over development. Furthermore, astroglial cells express steroid hormone receptors and show rapid responses to hormonal manipulations, however, despite important sex differences in telencephalic regions such as the cortex and hippocampus few studies have examined sex differences in astroglial cells in development and outside of the hypothalamus and amygdala. To phenotype cortical astroglial cells across postnatal development while considering potential sex differences, we used translating ribosome affinity purification together with RNA sequencing (TRAPseq) and immunohistochemistry to phenotype the entire astroglial translatome in males and females at key developmental time points: P1, P4, P7, P14, P35 and in adulthood. Overall, we found two distinct astroglial phenotypes between early (P1-P7) and late development (P14-Adult). We also noted that although astroglia show few basal sex differences in adulthood, they show significant sex differences in developmental gene expression patterns, with peak sex differences observed at P7. At least part of the sex differences observed at P7 appear to be due to males reaching a more mature astroglial phenotype earlier than females. Together, these data clearly delineate and phenotype astroglia across development and identify sex differences in astroglial developmental programs. Importantly, these developmental sex differences could have an impact on the construction and maintenance of neuronal networks and potential developmental windows of vulnerability to neurologic and psychiatric disease.

neuroscience↗

bioRxiv2018

Epigenetic transmission of cardiometabolic risk in offspring discordant for maternal gestational metabolic fitness

OBJECTIVEDiabesity during gestation predisposes offspring to lifetime cardiometabolic risk. We demonstrated that maternal biliopancreatic diversion surgery (BPD) improved metabolic fitness and pregnancies reducing cardiometabolic risk in siblings born after (AMS) compared to before maternal surgery (BMS). We found differential methylation of inflammatory and glucoregulatory genes in peripheral blood cell DNA in offspring and in mothers after BPD compared to preoperative \"control\" women. Here we study offspring trajectories of cardiometabolic risk markers and determine persistence of the methylome related to body weight (BMI) and gestational weight gain (GWG).\n\nRESEARCH DESIGN AND METHODSProspective, cross-sectional study of 133 mothers with 89 BMS and 183 AMS offspring born mean 4 years after BPD and 83 unoperated control women was conducted, and differential methylation patterns in mothers were compared with those of offspring during 2-26 years.\n\nRESULTSIndependent of maternal or offspring BMI and GWG, postoperative maternal metabolic fitness was associated with improved cardiometabolic phenotype in AMS vs. BMS offspring sustained beyond puberty. BMS offspring exhibited increasing linear trajectories of weight, cardiometabolic and inflammation risk factors versus normative horizontal trajectories of AMS offspring. Methylation differences between AMS and BMS offspring identified 45 625 differentially methylated sites, 73% overlapping with those of mothers vs. controls; 4 446 demonstrated similar sustained directionality of differences in methylation levels; 154 sites exhibited significant correlation coefficients (r[≥]0.4) overrepresented within genes associated with cardiometabolic risk, growth and inflammation.\n\nCONCLUSIONMaternal BPD appears to epigenetically prevent transmission of cardiometabolic risk independent of BMI.

developmental biology↗