Biology subjects

Drouin, S.

Publications and source records attributed to Drouin, S..

4 recordsLinked to original sources

bioRxiv2026

A novel machine-learning classification model detects oxidative fiber type transitions in a rabbit model of cerebral palsy

The distribution of slow-and fast-twitch fiber types in a skeletal muscle heavily influences its physiology. Muscle biopsy studies indicate atypical fiber type composition and fiber size variation in children with cerebral palsy (CP), but subjects have variable treatment history and a variety of muscles affected, so uncertainties remain. In this study, we developed a novel machine-learning classification model to perform high-throughput fiber typing of complete transverse muscle sections. Our XGBoost algorithm-based prediction model yielded a balanced accuracy score of 0.89 and a macro F1-score of 0.89, reflecting its ability to robustly predict muscle fiber type from myosin heavy chain (MyHC) isoform immunofluorescence intensities and morphological descriptors. This is the first reported fiber type classifier to consider hybrid fibers, which is a major advance, considering at least 20% of myofibers are hybrid yet they are routinely overlooked due to difficulty in their detection. We used this classification model to define fiber types of more than 7 million myofibers from flexor-extensor muscle pairs in rabbits that experienced hypoxia-ischemia (HI) injury in utero (modeling CP), and typically developing sham rabbits. We observed an oxidative fiber type shift in flexor muscles (biceps brachii and tibialis anterior) of HI rabbits at postnatal day (P)14-20 and P30-32 (weaning age). This altered fiber type composition imparts reduced contractile force and is amenable to sustained muscle activity; it may reflect chronic low-frequency motor unit activation. This work supports prior clinical reports that developmental trajectories of muscle fibers are disrupted in CP.

neuroscience↗

bioRxiv2026

Inter-individual variation of cellular and gene-expression properties of the human striatum

The human brain varies from person to person in ways that shape behaviors and vulnerabilities, yet the cellular and molecular bases for inter-individual variation are largely unknown. Here we describe an analysis of cellular and gene-expression variation in four key structures of the striatum complex - the caudate, putamen, nucleus accumbens, and internal capsule - as well as the prefrontal cortex, from single-nucleus RNA-seq analysis of 3.9 million nuclei from 178 adult brain donors. We found that people with more astrocytes in any one brain region tended to have this property in all brain regions sampled; the same was true of striatal interneurons, microglia, and oligodendrocyte precursor cells (OPCs). OPCs showed attrition with age, declining in numbers by approximately 40% between age 30 and age 80 in both gray matter and white matter regions. We identified thousands of age-associated (but few sex-associated) variations in gene expression; the vast majority of these effects of age were cell-type-specific. Aging most strongly affected gene expression in projection neurons - especially striatal medium spiny neurons (MSNs/SPNs) - and had a much smaller effect on gene expression in interneurons. Individuals ages could be predicted to within about five years based on RNA-expression patterns from any of the striatal cell types. Common genetic variants detectably affected the expression levels of some ten thousand genes; the great majority of these effects were cell-type-specific. These data will provide a foundation for exploring natural inter-individual variation, aging, and tissue-based studies of human brain vulnerabilities.

neuroscience↗

bioRxiv2026

Mesoscale molecular architecture of the human striatum across cell types and lifespan

The human striatum is a central hub for a diverse array of motor, cognitive, and affective behaviors, yet it lacks obvious cytoarchitectural boundaries that define functional territories. Here, we uncover a robust and molecularly defined mesoscale architecture in the human striatum. Using Slide-tags, a scalable single-nucleus spatial transcriptomics technology, we profiled 1.1 million cells across the full span of the anterior striatum of 19 postmortem donors, spatially mapping all striatal populations. Our data uncover a natural subdivision of the striatum into six zones, each defined by molecularly distinct populations of medium spiny neurons, and featuring spatially coordinated neuron-astrocyte signaling. Relative to MSNs in ventral zones, MSNs in dorsal zones exhibit higher expression of genes for synaptic remodeling and plasticity via ephrin and TGF-beta, while the ventral zone is defined by greater expression of semaphorin, protein chaperone, and hedgehog signaling pathways. By imputing zonal identities onto a larger single-nucleus RNA-seq cohort of 131 donors, we find that the dorsal zones exhibit greater age-related transcriptional changes, and that overall, the gene-expression differences that define spatial zonation patterns are attenuated with advancing age. This atlas provides a mesoscale molecular definition of human striatal anatomy, linking cell type identity to functional specialization and aging susceptibility.

neuroscience↗

bioRxiv2022

Genome-wide CRISPR Screens Identify Ferroptosis as a Novel Therapeutic Vulnerability in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most frequent cancer diagnosed in children. Despite the great progress achieved over the last 40 years, with cure rates now exceeding 85%, refractory or relapsed ALL still exhibit a dismal prognosis. This poor outcome reflects the lack of treatment options specifically targeting relapsed or refractory ALL. To address this gap, we have performed whole-genome CRISPR/Cas drop-out screens on a panel of seven B-ALL cell lines. Our results demonstrate that while there was a significant overlap in gene essentiality between ALL cell lines and other cancer types survival of ALL cell lines was dependent on several unique metabolic pathways, including an exquisite sensitivity to GPX4 depletion and ferroptosis induction and GPX4 KO. Detailed molecular analysis of B-ALL cells suggest that they are primed to undergo ferroptosis as they exhibit high steady-state oxidative stress potential, a low buffering capacity, and a disabled GPX-independent secondary lipid peroxidation detoxification pathway. Finally, we validated the sensitivity of B-ALL to ferroptosis induction using patient-derived B-ALL samples.

cancer biology↗