Biology subjects

Michel, R.

Publications and source records attributed to Michel, R..

4 recordsLinked to original sources

bioRxiv2026

Senescent cell networks link matrix remodeling and vascular dysfunction in human fibroids

Uterine fibroids (leiomyomas) are highly prevalent benign tumors defined by excessive extracellular matrix (ECM) deposition, altered vascular structure, and progressive tissue stiffening, yet the cellular programs that coordinate these features remain poorly understood. Cellular senescence has been implicated in fibroid biology, but whether senescence represents a uniform state or distinct, functionally specialized cell identities within fibroids is unknown. Here, we identify the distinct heterogeneous populations of senescent cells ("senotypes") present in human fibroids and characterize their role in shaping the fibroid microenvironment. Using single-cell RNA sequencing (scRNA-seq) integrated with a senescence gene signature and protein-level validation, we identify senescent cells (SnC) distributed across fibroblast, mural, and endothelial compartments, each exhibiting distinct transcriptional programs. SnC endothelial cells (ECs) are enriched in fibroids relative to matched myometrium and activate TEAD4-associated mechanosensing, angiogenic, and immune signaling pathways, despite being associated with impaired vessel maturation in situ. In parallel, SnC fibroblast and mural populations in fibroids upregulated SRF-associated cytoskeletal and ECM programs, accompanied by increased COL6A3 expression and collagen VI deposition, consistent with tissue stiffening. Ligand-receptor and spatial analyses reveal that these SnC populations function as interconnected signaling hubs, coordinating immune cell recruitment and stromal remodeling. Importantly, analysis of human fibroids treated with collagenase demonstrated a reduction in both ECM density and SnC burden, supporting a reinforcing relationship between matrix mechanics and senescence. Together, these findings establish senescence in fibroids as a heterogeneous, mechanically reinforced, and network-driven process that links vascular dysfunction, immune signaling, and fibrosis, highlighting distinct SnC states as potential translational targets for non-surgical therapies.

cell biology↗

bioRxiv2026

Cancer-Associated Mesothelial Cells Drive Immune Escape and Therapy Resistance in Ovarian Cancer

Cancer-associated mesothelial cells (CAMCs) are key modulators of the ovarian tumor microenvironment, contributing to tumor growth an immune evasion. Normal mesothelial cells play a role in peritoneal homeostasis and immune surveillance and represent the first point of contact during abdominal dissemination of ovarian cancers. Yet, their role in ovarian tumor immunity remains poorly understood. Here, we map the cellular states, spatial organization, and immune functions of CAMCs across ovarian cancer progression. Using lineage tracing and spatial transcriptomics, we demonstrate that CAMCs originate from mesothelial cells at the tumor surface and can progressively infiltrate the tumor core, undergoing a phenotypic transition towards fibroblast-like and immunosuppressive states. We characterize the function of an unrecognized CAMC subtype marked by SERPINB2+ expression, and a combination of markers absent in normal mesothelial cells. CAMCSerpinb2+ cells have reduced expression of pro-inflammatory cytokines (IL-2, IL-7, IL-12, IL-15) and increased expression of IL-10, TGF{beta}1, and CCL17, promoting regulatory T cell recruitment and tolerogenic CD4+ T cell responses. Functionally, CAMCSerpinb2+ accelerate tumor growth, reduce CD4+ T and B cell infiltration, and expand Treg populations, ultimately leading to immunotherapy resistance. Together, our findings identify CAMCs as a potential therapeutic target in peritoneal carcinomatosis and as a means of restoring sensitivity to current treatments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/698232v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@14e9098org.highwire.dtl.DTLVardef@f6f929org.highwire.dtl.DTLVardef@601517org.highwire.dtl.DTLVardef@8cc7c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Alpha-band lateralization and microsaccades elicited by exogenous cues do not track attentional orienting

We explore the world by constantly shifting our focus of attention towards salient stimuli, and then disengaging from them in search of new ones. The alpha rhythm (8-13 Hz) has been suggested as a pivotal neural substrate of these attentional shifts, due to its local synchronization and desynchronization that suppresses irrelevant cortical areas and facilitates relevant areas, a phenomenon called alpha lateralization. Whether alpha lateralization tracks the focus of attention from orienting toward a salient stimulus to disengaging from it is still an open question. In this study, we addressed this question by leveraging the well-established phenomenon of Inhibition of Return (IOR), consisting of an initial facilitation in response times (RTs) for target stimuli appearing at an exogenously cued location, followed by a suppression of that location. Our behavioral data showed a typical IOR effect with both early facilitation and subsequent inhibition. By contrast, alpha was lateralized only in the cued direction, but never re-lateralized in a manner compatible with the behavioral inhibition effect. Importantly, also the initial lateralization towards the cue ocurred too late to account for the behavioral facilitation effect. Furthermore, we analyzed the interaction between alpha lateralization and microsaccades: at the same time when alpha was lateralized towards the cued location, microsaccades were mostly oriented away from the cued location. Crucially, the two phenomena showed a significant positive correlation. These results indicate that alpha lateralization reflects primarily the processing of salient stimuli, challenging the view that alpha lateralization is directly involved in exogenous attentional orienting per se. We discuss the relevance of the present findings for an oculomotor account of alpha lateralization as a modulator of cortical excitability in preparation of a saccade.

neuroscience↗

bioRxiv2020

Theta rhythmic attentional enhancement of alpha rhythmic perceptual sampling

Accumulating evidence suggests that visual perception operates in an oscillatory fashion at an alpha frequency (around 10 Hz). Moreover, visual attention also seems to operate rhythmically, albeit at a theta frequency (around 5 Hz). Both rhythms are often associated to "perceptual snapshots" taken at the favorable phases of these rhythms. However, less is known about the unfavorable phases: do they constitute "blind gaps," requiring the observer to guess, or is information sampled with reduced precision insufficient for the task demands? As simple detection or discrimination tasks cannot distinguish these options, we applied a continuous report task by asking for the exact orientation of a Landolt rings gap to estimate separate model parameters for precision and the amount of guessing. We embedded this task in a well-established psychophysical protocol by densely sampling such reports across 20 cue-target stimulus onset asynchronies in a Posner-like cueing paradigm manipulating involuntary spatial attention. Testing the resulting time courses of the guessing and precision parameters for rhythmicities using a fast Fourier transform, we found an alpha rhythm (9.6 Hz) in the precision parameter and a theta rhythm (4.8 Hz) in the guess rate for invalidly cued trials. These results indicate that the perceptual alpha rhythm reflects fluctuations in spatial resolution, while the attentional theta rhythm provides periodic enhancement of this resolution. We propose a tentative model for this interplay and argue that both rhythms result in an environmental sampling characterized by fluctuating spatial resolution, speaking against a strict succession of blind gaps and perceptual snapshots.

neuroscience↗