Paula Lépine

Montreal Neurological Institute and Hospital

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Thomas M. Durcan

Structural Genomics Consortium

Meghna Mathur

Montreal Neurological Institute and Hospital

Nguyen‐Vi Mohamed

McGill University

Edward A. Fon

Montreal Neurological Institute and Hospital

Julien Sirois

Montreal Neurological Institute and Hospital

Carol X.‐Q. Chen

McGill University

Lenore K. Beitel

McGill University

Rhalena A. Thomas

Montreal Neurological Institute and Hospital

María Lacalle‐Aurioles

McGill University

Vincent Soubannier

McGill University

Cooperative Institutions

McGill University

Montreal Neurological Institute and Hospital

Centre Hospitalier de l’Université de Montréal

University of Chicago Medical Center

Drug Discovery Laboratory (Norway)

University of California, Davis

Université de Montréal

Centre National de la Recherche Scientifique

McGill University Health Centre

University of California System

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The problem of polio and the direction of research.

Paula Lépine

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CelltypeR: A flow cytometry pipeline to annotate, characterize and isolate single cells from brain organoids

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Rhalena A. Thomas Julien Sirois Shu‐Ming Li Alexandre Gestin Ghislaine Deyab

Abstract Motivated by the growing number of single cell RNA sequencing datasets (scRNAseq) revealing the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a high-throughput, standardized approach for reproducibly characterizing cell types in complex neuronal tissues based on protein expression levels. Our approach combines a flow cytometry (FC) antibody panel targeting brain cells with a computational pipeline called CelltypeR, with functions for aligning and transforming datasets, optimizing unsupervised clustering, annotating and quantifying cell types, and statistical comparisons. We applied this workflow to human iPSC-derived midbrain organoids and identified the expected brain cell types, including neurons, astrocytes, radial glia, and oligodendrocytes. Defining gates based on the expression levels of our protein markers, we performed Fluorescence-Activated Cell Sorting of astrocytes, radial glia, and neurons, cell types were then confirmed by scRNAseq. Among the sorted neurons, we identified three subgroups of dopamine (DA) neurons; one reminiscent of substantia nigra DA neurons, the cell type most vulnerable in Parkinson’s disease. Finally, we use our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets.

Cell type

Organoid

Cell Sorting

10.1101/2022.11.11.516066

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The Technique of Red Cell Agglutination in the Diagnosis of Influenza.

Ann. Inst. Pasteur (1946)

Paula Lépine V. Sautter L. Reinié

Agglutination (biology)

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Rôle de la Galectin-3 extra cellulaire dans la migration des cellules B à travers les barrières du système nerveux central dans le contexte de la sclérose en plaques

Paula Lépine

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RESULTS OF THE FEASIBILITY STUDY OF A SYSTEM FOR WARNING OF DROWSINESS AT THE STEERING WHEEL BASED ON ANALYSIS OF DRIVER EYELID MOVEMENTS

Chantal Lavergne Paula Lépine P Artaud S Planque A Dômont

Renault has investigated two approaches for developing an on-board system to warn of driver drowsiness. The first approach is based on the use of mechanical signals (steering wheel angle, lateral position, etc.), while the second is based on analysis of eyelid movements. The aim of this system is to warn the driver sufficiently early of the occurrence of micro-sleeps, because it is during these micro-sleep phases that the driver completely loses control of his vehicle. These moments of loss of control of the vehicle are characterized objectively by the simultaneous analysis of physiological signals and driving incidents recorded during tests on simulator and on the test circuit. [A] For the covering abstract, see IRRD 896528.

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Citations (14)

[Action of salts on sedimentation rate of lipoproteins].

PubMed (1955)

P Slizewicz P Rebeyrotte Paula Lépine

Sedimentation

Erythrocyte sedimentation rate

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The problem of polio and the direction of research.

Paula Lépine

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[Selection by chromatography of poliomyelitis strains].

PubMed (1965)

J. L. Delsal Paula Lépine V. Sautter

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Midbrain organoids with an SNCA gene triplication model key features of synucleinopathy

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Nguyen‐Vi Mohamed Julien Sirois Janani Ramamurthy Meghna Mathur Paula Lépine

SNCA, the first gene associated with Parkinson′s disease, encodes the α-synuclein (α-syn) protein, the predominant component within pathological inclusions termed Lewy bodies (LBs). The presence of LBs is one of the classical hallmarks found in the brain of patients with Parkinson′s disease, and LBs have also been observed in patients with other synucleinopathies. However, the study of α-syn pathology in cells has relied largely on two-dimensional culture models, which typically lack the cellular diversity and complex spatial environment found in the brain. Here, to address this gap, we use 3D midbrain organoids (hMOs), differentiated from human induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These hMOs recapitulate key features of α-syn pathology observed in the brains of patients with synucleinopathies. In particular, we find that SNCA triplication hMOs express elevated levels of α-syn and exhibit an age-dependent increase in α-syn aggregation, manifested by the presence of both oligomeric and phosphorylated forms of α-syn. These phosphorylated α-syn aggregates were found in both neurons and glial cells and their time-dependent accumulation correlated with a selective reduction in dopaminergic neuron numbers. Thus, hMOs from patients carrying SNCA gene multiplication can reliably model key pathological features of Parkinson′s disease and provide a powerful system to study the pathogenesis of synucleinopathies.

Synucleinopathies

Organoid

10.1101/2021.04.12.439480

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RNA-binding protein altered expression and mislocalization in multiple sclerosis

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Katsuhisa Masaki Yoshifumi Sonobe Ghanashyam D. Ghadge Peter Pytel Paula Lépine

Abstract Objective Nuclear depletion and mislocalization of RNA-binding proteins (RBPs) trans-activation response DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS) are thought to contribute to the pathogenesis of a number of disorders, including amyotrophic lateral sclerosis (ALS). We recently found that TDP-43 as well as polypyrimidine tract binding protein (PTB) have decreased expression and mislocalization in oligodendrocytes in demyelinated lesions in an experimental mouse model of multiple sclerosis (MS) caused by Theiler’s murine encephalomyelitis virus infection. Methods The latter finding prompted us to investigate TDP-43, FUS, and PTB in the demyelinated lesions of MS and in in vitro cultured human brain-derived oligodendrocytes. Results We found: i) mislocalized TDP-43 in oligodendrocytes in active lesions in some MS patients; ii) decreased PTB1 expression in oligodendrocytes in mixed active/inactive demyelinating lesions; iii) decreased nuclear expression of PTB2 in neurons in cortical demyelinating lesions; iv) nuclear depletion of TDP-43 in oligodendrocytes under metabolic stress induced by low glucose/low nutrient conditions compared to optimal culture conditions. Conclusion TDP-43 has been found to have a key role in oligodendrocyte function and viability, while PTB is important in neuronal differentiation, suggesting that altered expression and mislocalization of these RBPs in MS lesions may contribute to the pathogenesis of demyelination and neurodegeneration. Our findings also identify nucleocytoplasmic transport as a target for treatment.

Pathogenesis

10.1101/829457

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