Biology subjects

Collin, A.

Publications and source records attributed to Collin, A..

13 recordsLinked to original sources

bioRxiv2026

An evolutionarily conserved interferon-responsive oligodendroglial state emerges during white matter aging

White matter dysfunction is a hallmark of brain aging and often precedes overt neurodegeneration, yet the cellular alterations connecting aging to white matter dysfunction remain poorly understood. Here, we establish the killifish optic nerve as a translational model of white matter aging by integrating transcriptomic, histological and ultrastructural analyses. This tissue recapitulates key molecular and structural features of mammalian white matter aging, including the depletion of oligodendroglial progenitor cells, metabolic dysfunction and reduced myelin thickness. Intriguingly, aging is also associated with the emergence of an interferon-responsive oligodendroglial state. This state is characterized by interferon response and antigen presentation programs that closely resemble those of pathology-associated oligodendroglia described in murine models of central nervous system disease. Our findings identify oligodendroglial dysfunction as a central feature of white matter aging and suggest that this age-associated oligodendroglial state emerges before overt neurodegeneration, providing a potential cellular link between aging and neurodegenerative diseases.

neuroscience↗

bioRxiv2026

A multimodal characterization of the human uncinate fasciculus

The uncinate fasciculus (UF) is a hook-shaped long-range association white matter tract that serves to bidirectionally transmit information between the anterior temporal lobe and the orbitofrontal cortex. Neuroimaging studies have suggested that changes in UF microstructure are involved in the neurobiological sequalae of childhood abuse (CA). Given that the UF is not present in rodents, it is vastly understudied with no cellular and molecular information available. To this end, we aimed to perform a multimodal characterization of the UF between individuals diagnosed with depression who died by suicide with (DS-CA) and without a history of severe CA (DS) and psychiatrically healthy individuals (CTRL). Fresh frozen UF tissue was obtained from the Douglas Bell-Canada Brain Bank, with phenotypic information collected via psychological autopsy. Immunohistochemistry with PDGFR and NogoA was used to label oligodendrocyte precursor cell (OPC) and oligodendrocyte (OL), respectively, and stereology was performed to ascertain cell density and soma volume. Single nucleus RNA sequencing (snRNAseq) was used to generate a transcriptomic survey of the cell types found in the UF. Finally, spectral focusing Coherent Anti-Stokes Raman Scattering (sf-CARS) microscopy was employed in tandem with a custom AxonDeepSeg segmentation model to measure axon diameter, myelin thickness, and g-ratio. No group differences were observed in histology or ultrastructure metrics, but nearly 50 differentially expressed genes (DEG) were identified between groups. Interestingly NECTIN3, the top DEG downregulated in OL1 and OL3 of DS-CA, is a computationally predicted target of the microRNA MIR646, the host gene of which was significantly downregulated in multiple cell types in DS-CA. Age-associated changes were pronounced and observed in all modalities, including an age-related increase in OL density, extensive changes in glial gene expression, as well as decreases in axon diameter and g-ratio. This study serves as a foundational resource on the molecular and cellular properties of the human UF. Our results suggest that observable myelin-related traces of depression or CA are limited in the UF and highlights the need for future research on the cellular and molecular properties of white matter tracts during aging.

neuroscience↗

bioRxiv2025

Ultrastructural Analysis of Human Uncinate Fasciculus with Spectral-Focusing Coherent Anti-Stokes Raman Spectroscopy

Characterizing the ultrastructure of myelin in the human brain is key to understanding the neurobiology of both health and disease. In postmortem human brain tissue, electron microscopy is often technically unfeasible due to poorer tissue quality. The uncinate fasciculus (UF) is a long-range white matter association tract that connects the anterior temporal lobe with the orbitofrontal cortex. The UF is not present in rodents yet is highly expanded in humans and non-human primates. As such, its molecular and ultrastructural properties are virtually unknown. Here, we develop and validate a novel spectral-focusing Coherent Anti-Stokes Raman Spectroscopy (sf-CARS) system coupled with a custom AxonDeepSeg segmentation model to characterize UF ultrastructure in the human postmortem brain (n=6). We provide a proof of concept of this new methodological pipeline in the UF temporal segment and observe that the mean axon diameter detected is 0.93 {micro}m {+/-} 0.54 and mean myelin thickness is 0.48 {micro}m {+/-} 0.14. We also observe that the UF axons are thicker than those in the anterior cingulate cortex white matter. We detail and validate the full methodology, including tissue fixation and sectioning, sf-CARS acquisition settings, as well as the AxonDeepSeg deep learning model parameters such that this pipeline can be utilized by others in the field.

neuroscience↗

bioRxiv2024

scMusketeers: Addressing imbalanced cell type annotation and batch effect reduction with a modular autoencoder

The growing number of single-cell gene expression atlases available offers a conceptual framework for improving our understanding of physio-pathological processes. To take full advantage of this revolution, data integration and cell annotation strategies need to be improved, in particular to better detect rare cell types and by better controlling batch effects in experiments. scMusketeers is a deep learning model that optimises the representation of latent data and solves both challenges. scMusketeers features three modules: (1) an autoencoder for noise and dimensionality reductions; (2) a focal loss classifier to enhance rare cell type predictions; and (3) an adversarial domain adaptation (DANN) module for batch effect correction. Benchmarking against state-of-the-art tools, including the UCE foundation model, showed that scMusketeers performs on par or better, particularly in identifying rare cell types. It also allows to transfer cell labels from single-cell RNA sequencing to spatial transcriptomics. With its modular and adaptable design, scMusketeers offers a versatile framework that can be generalized to other large-scale biological projects requiring deep learning approaches, establishing itself as a valuable tool for single-cell data integration and analysis.

bioinformatics↗

bioRxiv2023

Translational mapping of spatially resolved transcriptomes in human and mouse pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis and limited treatment options. Efforts to identify effective treatments are thwarted by limited understanding of IPF pathogenesis and poor translatability of available preclinical models. To address these limitations, we generated spatially resolved transcriptome maps of human IPF and bleomycin-induced mouse lung fibrosis. We uncovered distinct fibrotic niches in the IPF lung, characterized by aberrant alveolar epithelial cells in a microenvironment dominated by TGF{beta} signaling alongside factors such as p53 and ApoE. We also identified a clear divergence between the arrested alveolar regeneration in the IPF fibrotic niches, and the active tissue repair in the acutely fibrotic mouse lung. Our study offers in-depth insights into the IPF transcriptional landscape and proposes alveolar regeneration as a promising therapeutic strategy for IPF.

molecular biology↗

bioRxiv2023

Deciphering circulating tumor cells binding in a microfluidic system thanks to a parameterized mathematical model

The spread of metastases is a crucial process in which some questions remain unanswered. In this work, we focus on tumor cells circulating in the bloodstream, the so-called Circulating Tumor Cells (CTCs). Our aim is to characterize their trajectories under the influence of hemodynamic and adhesion forces. We focus on already available in vitro measurements performed with a microfluidic device corresponding to the trajectories of CTCs - without or with different protein depletions - interacting with an endothelial layer. A key difficulty is the weak knowledge of the fluid velocity that has to be reconstructed. Our strategy combines a differential equation model - a Poiseuille model for the fluid velocity and an ODE system for the cell adhesion model - and a robust and well-designed calibration procedure. The parameterized model quantifies the strong influence of fluid velocity on adhesion and confirms the expected role of several proteins in the deceleration of CTCs. Finally, it enables the generation of synthetic cells, even for unobserved experimental conditions, opening the way to a digital twin for flowing cells with adhesion.

cancer biology↗

bioRxiv2023

On-farm hatching and contact with adult hen post hatch induce sex-dependent effects on performance and welfare in broiler chickens

To improve the early perinatal conditions of broiler chicks, alternative hatching systems have been developed. On-farm hatching (OFH) with an enriched microbial and stimulating environment by the presence of an adult hen is a promising solution. Day-old chicks were allotted within five hatching and rearing conditions: OFH, conventional hatchery (CH), CH and post-hatching treatment with antibiotics (CH + AB), as well as both hatching systems with an adult hen at hatching (OFH + H, CH + H). To challenge the robustness of chickens, they were exposed on D27 to suboptimal rearing conditions by combining for 4 h transport in boxes in a new room at a lower temperature and fasting. On their return to the original room, the chicken density was increased, and birds were orally vaccinated with the Gumboro vaccine. The impacts of these conditions on hatchability, chick quality score, performance, health and robustness were determined. The OFH chick body weights (BWs) were significantly greater than those of CH chicks at hatching. Whereas there was no effect of hatching conditions, the presence of hens decreased the hatchability rate, the quality score of OFH chicks and increased mortality at hatching. Treatment of CH chicks with antibiotics (CH + AB) temporarily decreased chicken BW at D19, but the feed conversion ratio (FCR) was not modified. At D19, OFH chicks had the highest BW compared to the other groups, and the presence of hens at hatching harmed chicken BW regardless of the hatching condition and FCR. An interaction between the effect of experimental rearing conditions and chicken sex was observed later for BW. In males, the OFH chickens were the heaviest compared to the other groups at D34 but not at D56. The presence of hens negatively impacted CH chicken BW at D56. In females, there was no effect of hatching condition on the BWs at D34 and D56, and the presence of hens had a positive impact on OFH chicken BW. There was no effect of hatching conditions on health parameters. In conclusion, the OFH system was a hatching system at least equivalent to the CH system. The presence of the hen at hatching and during the chick start-up phase on performance interacted with the hatching condition and the sex of the chickens.

physiology↗

bioRxiv2023

Thermal conditioning of quail embryos has transgenerational and reversible long-term effects

In the current context of global warming, thermal manipulation of avian embryos has received increasing attention as a strategy to promote heat tolerance in avian species by simply increasing the egg incubation temperature. However, because of their likely epigenetic origin, thermal manipulation effects may last more than one generation with consequences for the poultry industry. We found that thermal manipulation repeated during 4 generations had an effect on hatchability, body weight, and weight of eggs laid in Japanese quails, with some effects increasing in importance over generations. Moreover, we show that the effects on body weight and egg weight can be transmitted transgenerationally, suggesting non-genetic inheritance mechanisms. This hypothesis is reinforced by the observed reversion of the effect on growth after five unexposed generations. Interestingly, we demonstrate a non-transgenerational effect of thermal manipulation on heat tolerance few days after hatch. In conclusion, our multigenerational study suggests a quantitative, transgenerational and reversible effect of thermal manipulation.

physiology↗

bioRxiv2022

An integrated cell atlas of the human lung in health and disease

Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.

cell biology↗

bioRxiv2019

A novel imaging biomarker for survival prediction in EGFR-mutated NSCLC patients treated with TKI

EGFR-mutated non-small cells lung carcinoma are treated with Tyrosine Kinase Inhibitors (TKI). Very often, the disease is only responding for a while before relapsing. TKI efficacy in the long run is therefore challenging to evaluate. Our objective is to derive a new imaging biomarker that could offer better insights on the disease response to treatment. This study includes 17 patients diagnosed as EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI. The early response to treatment is evaluated with 3 computed tomography (CT) scans of the primitive tumor (one before the TKI introduction and two after). Using our knowledge of the disease, an imaging biomarker based on the tumor heterogeneity evolution between the first and the third exams is defined and computed using a novel mathematical model calibrated on patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker (p = 0.009). Using the ROC curve, the patients are separated into two populations hence the comparison of the survival curves is statistically significant (p = 0.025). Initial state of the tumor seems to have a role for the prognosis of the response to TKI treatment. More precisely, the imaging marker - defined using only the CT scan before the TKI introduction - allows us to determine a first classification of the population which is refined over time using the imaging marker as more CT scans become available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.

cancer biology↗

bioRxiv2018

Spontaneous intake and long-term effects of essential oils after a negative postnatal experience in chicks

The postnatal period is critical for broiler chicks as they are exposed to, possibly stressful, environmental changes in the hatchery and during transportation to the rearing houses. The ability of broiler chicks to spontaneously drink essential oils (EO) to mitigate the effects of a negative postnatal experience was tested. Chicks were either immediately placed in the rearing facility (C group), or subjected to a 24h-delay period before their placement (D group), mimicking the possible transportation delay in commercial conditions.\n\nIn experiment 1, each group had access to either water only or to water and one EO (cardamom, marjoram or verbena) from D1 to D13. The verbena EO intake was higher in the D group than in the C group from D1 to D6 and the cardamom EO intake was lower in the D group than in the C group from D6 to D13.\n\nIn experiment 2, half of the groups had access to water only and the other half was offered water and the 3 EO simultaneously. The EO were not differently chosen by chicks between D and C groups except a lower cardamom EO intake was observed in the D group than in the C group from D6 to D12. The delayed placement of the D group reduced chicken growth until 34 days of age and temporarily increased the feed conversion ratio, but did not affect their welfare or the prevalence of health disorders. The EO intake did not allow the chicks in the D group to overcome the growth reduction, but did overcome the reduction in Pectoralis major muscle yield. In conclusion, chicks are able to make spontaneous choices regarding EO intake according to their postnatal experience when EO are presented individually, but in our experimental design, they were not when EO were simultaneously presented. The EO intake only partially mitigated the decrease in chicken performance after the negative postnatal experience.

animal behavior and cognition↗

bioRxiv2018

Onecut factors and Pou2f2 regulate diversification and migration of V2 interneurons in the mouse developing spinal cord

Acquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.\n\nSignificance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

developmental biology↗

bioRxiv2017

Muscle transcriptome analysis reveals molecular pathways and biomarkers involved in extreme ultimate pH and meat defect occurrence in chicken

The processing ability and sensory quality of chicken breast meat are highly related to its ultimate pH (pHu), which is mainly determined by the amount of glycogen in the muscle at death. To unravel the molecular mechanisms underlying glycogen and meat pHu variations and to identify predictive biomarkers of these traits, a transcriptome profiling analysis was performed using an Agilent custom chicken 8x60K microarray. The breast muscle gene expression patterns were studied in two chicken lines experimentally selected for high (pHu+) and low (pHu-) pHu values of the breast meat. Across the 1,436 differentially expressed (DE) genes found between the two lines, many were involved in biological processes related to muscle development and remodelling and carbohydrate and energy metabolism. The functional analysis showed an intensive use of carbohydrate metabolism to produce energy in the pHu- line, while alternative catabolic pathways were solicited in the muscle of the pHu+ broilers, compromising their muscle development and integrity. After a validation step on a population of 278 broilers using microfluidic RT-qPCR, 20 genes were identified by partial least squares regression as good predictors of the pHu, opening new perspectives of screening broilers likely to present meat quality defects.

genomics↗