Biology subjects

Jacques, C.

Publications and source records attributed to Jacques, C..

7 recordsLinked to original sources

bioRxiv2025

Endothelin Signaling via EDNRB receptor Reduces Proliferation and Promotes Proneural-to-Mesenchymal Transition in Gliomas

Diffuse gliomas are incurable primary brain tumors encompassing three histo-molecular subtypes: glioblastomas (GB), astrocytomas, and oligodendrogliomas. The latter two harbor IDH1 mutations and exhibit slower progression than glioblastomas. Diffuse gliomas are composed of highly plastic tumor cells capable of transitioning between astrocyte-like, oligodendrocyte-like, progenitor-like, and mesenchymal-like states, driven by genetic alterations and microenvironmental cues. The proneural-to-mesenchymal transition (PMT), associated with increased malignancy, is notably influenced by cytokines in the tumor microenvironment. Endothelin cytokines (ET-1, ET-2, ET-3), primarily secreted by vascular cells, regulate not only vascular tone but also astrocyte and neural stem cell proliferation via the G-protein-coupled receptors EDNRA and EDNRB. Prior studies using serum-cultured glioma lines suggested pro-proliferative effects of endothelins; however, such models poorly recapitulate the in vivo glioma context. In this study, we comprehensively revisited endothelin signaling - covering receptor expression, regulation, downstream pathways, and cellular responses-using eleven serum-free, patient-derived glioma lines (glioblastomas, IDH-wt and IDH-mutant oligodendrogliomas and astrocytomas), along with primary tumor samples. Multi-omics and electrophysiological analyses revealed EDNRB as the predominant receptor, enriched in astrocyte-like cells, upregulated by BMPs or growth factor withdrawal, and downregulated by interferons, IL-6 cytokines, endothelins, and Hippo/YAP activation. In contrast, EDNRA was expressed by a perivascular tumor subpopulation and induced by Notch signaling in glioblastomas but not in IDH1-mutant cells. Functionally, endothelins reduced proliferation across all models while promoting migration and PMT. Mechanistically, EDNRB activation increased intracellular Ca{superscript 2} and activated ERK, STAT3, and apamin-sensitive SK2/SK3 potassium channels. These findings identify endothelin signaling as an important regulator of glioma cell plasticity and behavior. HighlightsO_LIEDNRB is the predominant endothelin receptor expressed in glioma cells, with a small subset of tumor cells expressing EDNRA in close proximity to blood vessels C_LIO_LIEndothelin signaling reduces proliferation while promoting cell migration and Proneural-to-Mesenchymal transition C_LIO_LIEndothelin activates downstream Ca2+, K+, ERK, and STAT3 signaling pathways C_LIO_LIEDNRB expression is both positively and negatively regulated by inflammatory cytokines and the Hippo/YAP1 pathway, whereas EDNRA is upregulated by Notch signaling and hypoxia C_LI

cancer biology↗

bioRxiv2025

Concurrent category-selective neural activity across the ventral occipito-temporal cortex supports a non-hierarchical view of human visual recognition

Visual recognition is a fundamental human brain function, supported by a network of regions in the ventral occipito-temporal cortex (VOTC). This network is thought to be organized hierarchically, with definite processing stages increasing in invariance and time-course from posterior to anterior cortical regions. Here we provide a stringent test of this view by measuring category-selective neural activity to natural images of faces across the VOTC with electrophysiological intracerebral recordings in a large human sample (N=140; >11000 recording sites). Face-selective high frequency broadband (30-160 Hz) neural activity is distributed across the VOTC, with right-hemispheric dominance and regional peaks of activity. Crucially, while a progressive increase in degree of category-selectivity is found along the postero-anterior axis, neural activity occurs largely concurrently ([~]100ms onset - [~]450ms offset) across all VOTC regions. These observations challenge the standard hierarchical view of neural organization of visual object recognition in the human association cortex, supporting alternative models of this key brain function.

neuroscience↗

bioRxiv2023

Aging and freezing of active nematic dynamics of cancer-associated fibroblasts by fibronectin matrix remodeling

Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in tumor stroma. Exhibiting an elongated morphology, CAFs align with each other, closely resembling nematic ordering in liquid crystal physics. CAFs play a pivotal role in the genesis and remodeling of the extracellular matrix (ECM), with ECM proteins, especially fibronectin, reciprocally modulating CAF alignment and coherence. Yet, the intricate feedback loops between fibronectin deposition and CAF structuring remain largely unexplored. Here, we combined CAF live imaging, traction force microscopy, ECM microfabrication, and theoretical modeling to assess how the ECM influences the dynamics of nematically ordered CAFs. We found that CAFs dynamically orchestrate a fibronectin network that mirrors their nematic ordering. Over time, this passive nematic ordering of fibronectin, in turn, steers CAF rearrangement. Contrary to most cellular systems, where defects remain dynamic at a steady state, the ECM/CAF interplay profoundly alters the behavior of both CAF and ECM nematics, leading to aging-massive slowdown, and even freezing of defect dynamics. This results in a CAFs capsule where aligned areas and defects are spatially and temporally fixed, yet active, exerting forces at the substate and transmitting forces between cells. Functionally, while defects may be permissive, it is the fibronectin loss-induced fluidization of the CAF capsule that critically undermines its barrier function.

cell biology↗

bioRxiv2022

Low and high frequency intracranial neural signals match in the human associative cortex

In vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (<30 Hz, LF) and broadband activity in the higher end of the frequency spectrum (>30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure selective responses to complex ecologically salient visual stimuli - human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.

neuroscience↗

bioRxiv2020

Dissociated face- and word-selective intracerebral responses in the human ventral occipito-temporal cortex

The extent to which faces and written words share neural circuitry in the human brain is actively debated. Here we compared face-selective and word-selective responses in a large group of patients (N = 37) implanted with intracerebral depth electrodes in the ventral occipito-temporal cortex (VOTC). Both face-selective (i.e., significantly different responses to faces vs. nonface visual objects) and word-selective (i.e., significantly different responses to words vs. pseudofonts) neural activity is isolated through frequency-tagging. Critically, this sensitive approach allows to objectively quantify category-selective neural responses and disentangle them from general visual responses. About 70% of significant contacts show either only face-selectivity or only word-selectivity, with the expected right and left hemispheric dominance, respectively. Spatial dissociations are also found within core regions of face and word processing, with a medio-lateral dissociation in the fusiform gyrus (FG) and surrounding sulci, while a postero-anterior dissociation is found in the inferior occipital gyrus (IOG). Only 30% of the significant contacts show both face- and word-selective responses. Critically, in these contacts, across the VOTC or in the FG and surrounding sulci, between-category selective-amplitudes (faces vs. words) showed no-to-weak correlations, despite strong correlations in both the within-category selective amplitudes (face-face, word-word) and the general visual responses to words and faces. Overall, we conclude that category-selectivity for faces and written words is largely dissociated in the human VOTC. Significance StatementIn modern human societies, faces and written words have become arguably the most significant stimuli of the visual environment. Despite extensive research in neuropsychology, electroencephalography and neuroimaging over the past three decades, whether these two types of visual signals are recognized by similar or dissociated processes and neural networks remains unclear. Here we provide an original contribution to this outstanding scientific issue by directly comparing frequency-tagged face- and word-selective neural responses in a large group of epileptic patients implanted with intracerebral electrodes covering the ventral occipito-temporal cortex. While general visual responses to words and faces show significant overlap, the respective category-selective responses are neatly dissociated in spatial location and magnitude, pointing to largely dissociated processes and neural networks.

neuroscience↗

bioRxiv2019

JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage

Ribosomal DNA (rDNA) is the most transcribed genomic region and contains hundreds of tandem repeats. Maintaining these rDNA repeats as well as the level of rDNA transcription is essential for cellular homeostasis. DNA damages generated in rDNA need to be efficiently and accurately repaired as rDNA repeats instability has been reported in cancer, aging and neurological diseases. Here, we describe that the histone demethylase JMJD6 is rapidly recruited at nucleolar DNA damage and is crucial for the relocalisation of rDNA in nucleolar caps. Yet, JMJD6 is dispensable for rDNA transcription inhibition. Mass spectrometry study revealed that JMJD6 interacts with the nucleolar protein Treacle and modulates its interaction with NBS1. Moreover, cells deficient for JMJD6 show increased sensitivity to nucleolar DNA damage as well as loss and rearrangements of rDNA repeats upon irradiation. Altogether our data reveals that rDNA transcription inhibition is uncoupled from rDNA relocalisation into nucleolar caps and that JMJD6 is required for rDNA stability upon the rDNA damage response through its role in nucleolar caps formation.\n\nAuthor summaryRibosomal DNA is the most transcribed genomic region composed of repeated sequences. Transcribed rDNA is essential for cellular homeostasis and cell proliferation. Numerous pathologies such as cancer and neurological disorders are described to present defective rDNA repeats maintenance. The mechanisms involved in the control of rDNA integrity involve major DNA repair pathways such as NonHomologous End-Joining and Homologous Recombination. However, how they are controlled and orchestrated is poorly understood. Here, we identified JMJD6 as a new member of the maintenance of rDNA integrity. We observed that JMJD6 controls the recruitment of NBS1 in the nucleolus in order to lead to the proper response to DNA damage at rDNA repeats.\n\nAuthor contributionsYC and DT wrote the manuscript with input from their coauthors. JF, CC, JH, S-KM, JL, J-PL and YC performed the experiments. JC supervised JF and JH during purification and mass spectrometry analysis. YC and DT conceived the project, designed research and coordinated the studies.

cell biology↗

bioRxiv2019

Diverse temporal dynamics of repetition suppression revealed by intracranial recordings in human ventral temporal cortex

Repeated stimulus presentations commonly produce decreased neural responses - a phenomenon known as repetition suppression (RS) or adaptation - in ventral temporal cortex (VTC) in humans and nonhuman primates. However, the temporal features of RS in human VTC are not well understood. To fill this gap in knowledge, we utilized the precise spatial localization and high temporal resolution of electrocorticography (ECoG) from 9 human subjects implanted with intracranial electrodes in VTC. Subjects viewed non-repeated and repeated images of faces with long-lagged intervals and many intervening stimuli between repeats. We report three main findings: (i) robust RS occurs in VTC for activity in high-frequency broadband (HFB), but not lower frequency bands, (ii) RS of the HFB signal is associated with lower peak magnitude, lower total responses, and earlier peak responses, and (iii) RS effects occur early within initial stages of stimulus processing and persist for the entire stimulus duration. We discuss these findings in the context of early and late components of visual perception, as well as theoretical models of repetition suppression.

neuroscience↗