Biology subjects

Lemoine, M.

Publications and source records attributed to Lemoine, M..

8 recordsLinked to original sources

bioRxiv2026

A multimodal single-cell atlas of the adolescent brain reveals gene regulatory networks linking development to disease risk

Adolescence represents a critical window of brain maturation when many neuropsychiatric disorders first emerge, yet the molecular mechanisms driving this developmental period remain incompletely understood. To address this gap, we generated a high-resolution multimodal cell atlas of the developing adolescent brain using paired single-nucleus RNA and ATAC sequencing (snRNA-seq + snATAC-seq) from cortex, hippocampus, and amygdala tissue of six donors aged 6-15 years, profiling 88,658 high-quality nuclei. Integrative analyses identified 36 enhancer-driven gene regulatory networks (eGRNs) with significant age-dependent dynamics in the transition from childhood to adolescence. The majority of adolescence-associated eGRNs were active in oligodendrocytes and their precursors, reflecting active oligodendrogenesis and myelin remodeling during this developmental period. Notably, age-associated cis-regulatory elements were enriched for expression quantitative trait loci (eQTLs) and colocalized with genetic variants linked to both neurodevelopmental and neurodegenerative disorders, suggesting that regulatory networks may be shared across normal adolescent brain development and disease vulnerability. This multimodal cell atlas provides a valuable resource for understanding the human adolescent brain and offers new insights into the molecular origins of neuropsychiatric disorders.

neuroscience↗

bioRxiv2024

Cell type mapping of mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy using single-nucleus multiomics

ObjectiveMild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) are brain lesions associated with focal epilepsy and characterized by increased oligodendroglial density, heterotopic neurons, and hypomyelination in the white matter. While previous studies have implicated somatic mutations in the SLC35A2 gene, the cellular and molecular mechanisms underlying MOGHE pathogenesis remain elusive. To address this gap, this study aimed to systematically characterize the cell type composition and molecular alterations of MOGHE lesions at cellular resolution using single-nucleus multiomics profiling. MethodsWe performed single-nucleus multiomics sequencing to obtain paired gene expression and chromatin accessibility profiles of > 31,000 nuclei from gray matter and white matter regions of MOGHE lesions, and compared the results with publicly available neurotypical control datasets. ResultsThe analysis of gray and white matter regions from two MOGHE patients revealed significant cellular composition alterations, including the presence of heterotopic neurons and disease-specific oligodendrocytes populations within the subcortical white matter. MOGHE-specific oligodendrocytes were characterized by the upregulation of synaptic functions and enhanced neuron communication, denoting a possible role in synaptic support and the mediation of glial-neuron interactions in the disease. On the other hand, MOGHE heterotopic neurons were characterized by the upregulation of genes associated with neuronal migration and the Wnt signaling pathway, suggesting a mechanism underlying their atypical localization. SignificanceThis high-resolution cell type mapping of MOGHE lesions in clinical samples unveils neuronal and glial populations affected by the disease, and provides novel insights into the pathophysiological mechanisms of MOGHE. Key PointsO_LIWe provide a multimodal cellular atlas of the human cortical and subcortical regions affected in MOGHE C_LIO_LIMOGHE-associated oligodendrocytes showed upregulation of synaptic functions and enhanced neuron communication C_LIO_LINeuronal migration and Wnt signaling are upregulated in MOGHE heterotopic neurons C_LI

neuroscience↗

bioRxiv2024

Temporal and spatial niche partitioning in a retrotransposon community of the Drosophila genome

Transposable elements (TEs), widespread genetic parasites, pose potential threats to the stability of their host genomes. Hence, the interactions observed today between TEs and their host genomes, as well as among the different TE species coexisting in the same host, likely reflect those that did not lead to the extinction of either the host or the TEs. It is not clear to what extent the expression and integration steps of the TE replication cycles are involved in this peaceful coexistence. Here, we show that four Drosophila LTR RetroTransposable Elements (LTR-RTEs), although sharing the same overall integration mechanism, preferentially integrate into distinct open chromatin domains of the host germline. Notably, the differential expressions of the gtwin and ZAM LTR-RTEs in ovarian and embryonic somatic tissues, respectively, result in differential integration timings and targeting of accessible chromatin landscapes that differ between early and late embryonic nuclei, highlighting connections between temporal and spatial LTR-RTEs niche partitionings.

genomics↗

bioRxiv2024

Multimodal single-cell sequencing of the human cortex reveals neuronal vulnerability and activated glial cell states in focal cortical dysplasia

Focal Cortical Dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-cell profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-cell dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a unique neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering new directions for targeted therapy development.

neuroscience↗

bioRxiv2024

Pervasive tissue-, genetic background-, and allele-specific gene expression effects in Drosophila melanogaster

The pervasiveness of gene expression variation and its contribution to phenotypic variation and evolution is well known. This gene expression variation is context dependent, with differences in regulatory architecture often associated with intrinsic and environmental factors, and is modulated by regulatory elements that can act in cis (linked) or in trans (unlinked) relative to the genes they affect. So far, little is known about how this genetic variation affects the evolution of regulatory architecture among closely related tissues during population divergence. To address this question, we analyzed gene expression in the midgut, hindgut, and Malpighian tubule as well as microbiome composition in the two gut tissues in four Drosophila melanogaster strains and their F1 hybrids from two divergent populations: one from the derived, European range and one from the ancestral, African range. In both the transcriptome and microbiome data, we detected extensive tissue- and genetic background-specific effects, including effects of genetic background on overall tissue specificity. Tissue-specific effects were typically stronger than genetic background-specific effects, although the two gut tissues were not more similar to each other than to the Malpighian tubules. An examination of allele specific expression revealed that, while both cis and trans effects were more tissue-specific in genes expressed differentially between populations than genes with conserved expression, trans effects were more tissue-specific than cis effects. Despite there being highly variable regulatory architecture, this observation was robust across tissues and genetic backgrounds, suggesting that the expression of trans variation can be spatially fine-tuned as well as or better than cis variation during population divergence and yielding new insights into cis and trans regulatory evolution. Author SummaryGenetic variants regulating gene expression can act in cis (linked) or in trans (unlinked) relative to the genes they affect and are thought to be important during adaptation because they can spatially and temporally fine-tune gene expression. In this study, we used the fruit fly Drosophila melanogaster to compare gene expression between inbred parental strains and their offspring in order to characterize the basis of gene expression regulation and inheritance. We examined gene expression in three tissues (midgut, hindgut, and Malpighian tubule) and four genetic backgrounds stemming from Europe and the ancestral range in Africa. Additionally, we characterized the bacterial community composition in the two gut tissues. We detected extensive tissue- and genetic background-specific effects on gene expression and bacterial community composition, although tissue-specific effects were typically stronger than genetic background effects. Genes with cis and trans regulatory effects were more tissue-specific than genes with conserved expression, while those with trans effects were more tissue-specific than those with cis effects. These results suggest that the expression of trans variation can be spatially fine-tuned as well as (or better than) cis variation as populations diverge from one another. Our study yields novel insight into the genetic basis of gene regulatory evolution.

evolutionary biology↗

bioRxiv2021

Elevational changes in bacterial microbiota structure and diversity in an arthropod-disease vector

Environmental conditions change rapidly along elevational gradients and have been found to affect community composition in macroscopic taxa, with lower diversity typically observed at higher elevations. In contrast, microbial community responses to elevation are still poorly understood. Specifically, the effects of elevation on vector-associated microbiota have not been studied to date, even though the within-vector microbial community is known to influence vector competence for a range of zoonotic pathogens. Here we characterize the structure and diversity of the bacterial microbiota in an important zoonotic disease vector, the sheep tick Ixodes ricinus, along replicated elevational gradient (630 - 1673 masl) in the Swiss Alps. 16S rRNA sequencing of the whole within-tick bacterial microbiota of questing nymphs and adults revealed a decrease in Faiths phylogenetic microbial alpha diversity with increasing elevation, while beta diversity analyses revealed a lower variation in microbial community composition at higher elevations. We also found a higher microbial diversity later in the season and significant differences in microbial diversity among tick life stages and sexes, with lowest microbial alpha diversity observed in adult females. No associations between tick genetic diversity and bacterial diversity were observed. Our study demonstrates systematic changes in tick bacterial microbiota diversity along elevational gradients. The observed patterns mirror diversity changes along elevational gradients typically observed in macroscopic taxa, and they highlight the key role of environmental factors in shaping within-host microbial communities in ectotherms.

ecology↗

bioRxiv2020

Alcohol boosts pheromone production in male flies and makes them sexier

The attraction of Drosophila melanogaster towards byproducts of alcoholic fermentation, especially ethanol, has been extensively studied 1-4. However, the adaptive value of this behavior has not been elucidated. Previous studies have suggested anthropomorphic interpretations of D. melanogaster behavior towards alcohols 5,6. Here, we instead assert that there exists a simple yet vital biological rationale for alcohol contact and consumption by these insects. We show that exposure to alcohols, especially methanol, results in an immediate amplification of fatty acid ester pheromone levels, which in turn elevates the probability that a male will successfully compete for a female during courtship. We proceed to identify three types of olfactory sensory neurons that detect ethanol and methanol. Moreover, we trace the ensuing neural circuits and reveal their role in controlling both attraction and aversion, where valence is balanced around mating status. Based on our results, we deduce that male flies associate with sources of alcohol as a biological imperative related to reproduction, and we provide an assessment of how and why D. melanogaster is associated with alcohol using a sound ecological and natural history approach to this previously enigmatic biological phenomenon. One sentence summaryFlies gain pheromone and courtship advantages with alcohol, but methanol is toxic, thus flies must balance risk versus reward.

neuroscience↗

bioRxiv2018

Does Borrelia burgdorferi sensu lato facilitate the colonisation of marginal habitats by Ixodes ricinus? A correlative study in the Swiss Alps

Parasites can alter host and vector phenotype and thereby affect ecological processes in natural populations. Laboratory studies have shown that Borrelia burgdorferi sensu lato, the causative agent of human Lyme borreliosis, induces physiological alterations in its main tick vector in Europe, Ixodes ricinus, which increase its survival under challenging conditions. We hypothesise that these phenotypic alterations may allow I. ricinus to colonise marginal habitats, thereby fuelling the ongoing range expansion of I. ricinus towards higher elevations and latitudes induced by climate change. To explore the potential for such an effect under natural conditions, we studied the prevalence of B. burgdorferi s.l. in questing I. ricinus and its variation with elevation in the Swiss Alps. We screened for B. burgdorferi s.l. infection in questing nymphs of I. ricinus (N = 411) from 15 sites between 528 and 1774 m.a.s.l to test if B. burgdorferi s.l. prevalence is higher at high elevations (i.e. in marginal habitats). We found that B. burgdorferi s.l. prevalence in I. ricinus nymphs decreased linearly with increasing elevation and that it was 12.6% lower in I. ricinus nymphs collected at high elevations compared to nymphs in the core range. Thus, we found no evidence that the B. burgdorferi s.l.-induced alterations of I. ricinus phenotype facilitate the colonisation of marginal habitats in the wild. These findings have implications for a better understanding of eco-evolutionary processes in natural host-parasite systems, as well as the assessment of Lyme borreliosis risk in regions where I. ricinus is newly emerging.

ecology↗