Biology subjects

Loulier, K.

Publications and source records attributed to Loulier, K..

5 recordsLinked to original sources

bioRxiv2026

Neocortical astrocyte diversity stems from distinct developmental origins

Key regulators of neural network activity in multiple advanced cognitive processes and essential components of the blood-brain barrier, astrocytes constitute a highly heterogeneous population at the morphological, molecular, and functional levels. However, how this diversity arises during mammalian brain development remains poorly investigated. Here, using a combination of multicolour genetic fate mapping, single-cell transcriptomic analyses, multichannel large-volume imaging and detailed 3D cell morphology reconstructions, we uncover a discrete subpopulation of neocortical astrocytes generated from an early restricted embryonic domain located outside of the dorsal pallium. Besides their separate lineage from pyramidal neurons, these astrocytes exhibit a developmental trajectory that differs from astrocytes produced by dorsal cortical progenitors, including different migratory pathways, spatial distributions and morphology. Overall, our results reveal the diversity of embryonic sources responsible for neocortical astrocyte genesis and provide key insights into the unsuspected complex developmental processes that underlie cortical astrocyte heterogeneity.

neuroscience↗

bioRxiv2026

Long-projection astrocytes challenge canonical territorial organization in the sleep-promoting VLPO

The ventrolateral preoptic nucleus (VLPO) is a key hypothalamic hub for non-rapid eye movement sleep, yet the glial architecture supporting its circuits remains poorly understood. Here, combining genetic labeling, high-resolution imaging and calcium imaging, we uncover unexpected astrocyte diversity in the VLPO. In addition to classical protoplasmic astrocytes, we identify paired "doublet" astrocytes associated with high local proliferative activity, as revealed by EdU incorporation. We further describe a population of long-projection astrocytes extending processes far beyond canonical astrocytic territories and contacting distant cells. These projections challenge the classical territorial organization of astrocytes and resemble morphologies previously thought to be restricted to hominid brains. Notably, VLPO astrocytes display robust spontaneous Ca{superscript 2} activity and a highly functionally connected network compared to astrocytes in the cortex and hippocampus. Together, these findings reveal specialized astrocyte architectures and enhanced glial network integration within a sleep-promoting nucleus. Reporting summaryBellier et al. identify three astrocyte subtypes in the sleep-promoting VLPO, including long-projection astrocytes with hominid-like morphology. They uncover marked postnatal gliogenesis, distinctive spontaneous Ca{superscript 2} dynamics, and tightly interconnected astrocytic networks, revealing region-specific astrocyte specialization and enhanced glial communication.

neuroscience↗

bioRxiv2025

Reversible multiscale corneal sexual dimorphism orchestrates neuro-epithelial coupling and tear proteome composition

Donor-recipient sex mismatch is an under-recognized risk factor for corneal graft rejection, yet the biological underpinnings at the ocular surface remain undefined. We hypothesized that sex hormones coordinately tune the tear-nerve-epithelium axis and that androgen exposure could normalize sex-linked differences relevant to alloimmune risk. We profiled 12-week-old mice in three hormonal contexts, i.e. male, female, and testosterone-treated female, combining tear biochemistry and label-free proteomics with epithelial lineage dynamics, in vivo sensory function, and corneal/trigeminal transcriptional readouts. Tear collection rate was comparable across groups, but total tear protein was reduced in females. Proteomics revealed extensive sex differences in extracellular composition, spanning lipid transport, protease-antiprotease balance, complement activity, and secretory/mucin pathways. Epithelial analyses showed sex-linked differences in progenitor output and spatial deployment, and sensory metrics indicated divergent innervation architecture and function. Across modalities, androgen supplementation in females shifted molecular and physiological profiles toward the male state, attenuating nearly all dimorphic signals, demonstrating that close to all sexual dimorphism observed here is reversible by testosterone and reflects an actively maintained endocrine state rather than a fixed developmental program. Complementary metabolite profiling provides a sex-stratified atlas of free modified nucleosides in tears, positioning extracellular epitranscriptomic markers as accessible indicators of hormonal context. Together, these results establish a multiscale, hormone-responsive sexual dimorphism at the ocular surface and offer a mechanistic framework linking sex and endocrine status to parameters that influence graft integration. They motivate sex-aware biomarkers, stratification by hormonal context in diagnostics and trials, and therapeutic strategies, including androgenic modulation, to mitigate the elevated rejection risk associated with sex mismatch in corneal transplantation.

physiology↗

bioRxiv2025

Decoding the molecular complexity governing corneal wound closure in vivo

The cornea, the transparent outermost layer of the eye, possesses exceptional wound healing capabilities essential for vision preservation. The complexity of the corneal microenvironment is central to its rapid healing; however, the molecular mechanisms orchestrating this process remain poorly defined, limiting therapeutic advancements. Here, we elucidate the extensive remodeling of the corneal molecular landscape following physical injury. Multi-omics analyses--including transcriptomic, epitranscriptomic, and proteomic profiling--uncover significant induction of epithelial cell plasticity driving wound closure. Moreover, lacrimal gland ablation further suppresses Pax6 expression, highlighting its regulatory role. Our multi-omic approach uniquely reveals bilateral remodeling of the molecular environment, a phenomenon constrained by an intact tear film. Collectively, our findings identify novel molecular factors critical to corneal healing, significantly advancing the understanding of epithelial plasticity. These insights will facilitate the translation of cell plasticity research into innovative strategies for tissue and organ regeneration.

physiology↗

bioRxiv2019

Direct readout of neural stem cell transgenesis with an integration-coupled gene expression switch

SUMMARYStable genomic integration of exogenous transgenes is critical for neurodevelopmental and neural stem cell studies. Despite the emergence of tools driving genomic insertion at high rates with DNA vectors, transgenesis procedures remain fundamentally hindered by the impossibility to distinguish integrated transgenes from residual episomes. Here, we introduce a novel genetic switch termed iOn that triggers gene expression upon insertion in the host genome, enabling simple, rapid and faithful identification of integration events following transfection with naked plasmids accepting large cargoes. In vitro, iOn permits rapid drug-free stable transgenesis of mouse and human pluripotent stem cells with multiple vectors. In vivo, we demonstrate accurate cell lineage tracing, assessment of regulatory elements and mosaic analysis of gene function in somatic transgenesis experiments that reveal new aspects of neural progenitor potentialities and interactions. These results establish iOn as an efficient and widely applicable strategy to report transgenesis and accelerate genetic engineering in cultured systems and model organisms.

developmental biology↗