Biology subjects

Lamy, C.

Publications and source records attributed to Lamy, C..

6 recordsLinked to original sources

bioRxiv2025

A single-nucleus multimodal framework reveals epigenomic priming of chemoresistant states in ovarian cancer

Non-genetic intratumor heterogeneity (ITH) drives therapeutic failure in cancer, yet its clinical monitoring remains challenging. We develop a multimodal single-nucleus framework that simultaneously profiles transcriptional and histone modification landscapes from frozen biopsies. Applied to longitudinal samples from 16 patients with high-grade serous ovarian cancer (HGSOC), this approach reveals reproducible tumor evolution under chemotherapy: proliferative and interferon-responsive states are lost, while those associated with TNF- and epithelial-mesenchymal transition (EMT) expand. Chromatin profiling shows that these chemoresistant programs are epigenetically primed through H3K4me1 marks before treatment and nominates transcription-factor drivers, including ZBTB7A. Non-genetic baseline tumor composition predicts survival, and fibroblast remodeling parallels malignant adaptation. These findings establish a clinically scalable strategy for mapping functional ITH and identify epigenomic priming as a determinant of therapeutic failure. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/692102v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@432524org.highwire.dtl.DTLVardef@3b7843org.highwire.dtl.DTLVardef@54a2eforg.highwire.dtl.DTLVardef@95273d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Motivational control is implemented by a cingulo-prefrontal pathway

The neuronal connections between the midcingulate cortex (MCC) and the dorsolateral prefrontal cortex (dlPFC) are associated with multiple cognitive functions, including rapid and long-term adaptive processes. Here we show that DREADD-mediated activation of MCC to dlPFC projection in macaques led to increased engagement in a foraging task, but did not alter their trial-to-trial adaptive strategy. We conclude that a critical role for MCC-dlPFC pathway is in the temporally extended control of behaviour rather than in rapid adaptation.

neuroscience↗

bioRxiv2024

Gadolinium-based nanoparticles AGuIX and their combination with ionizing radiation trigger AMPK-dependent proinflammatory reprogramming of tumor-associated macrophages

BackgroundTumor-associated macrophages (TAMs) are essential components of the inflammatory microenvironment of tumors and are associated with poor clinical outcomes in the majority of cancers. TAMs mainly exhibit anti-inflammatory functions that promote and support the tissue remodeling, the immune suppression and the tumor growth. Regarding their plasticity, the functional reprogramming of anti-inflammatory TAMs into proinflammatory phenotype recently emerged as a therapeutic opportunity to improve the effectiveness of anticancer treatments such as radiotherapy. ResultsHere we show that gadolinium-based nanoparticles AGuIX alone and in combination with ionizing radiation (IR) induce in a dose-dependent manner, the accumulation of DNA double strand breaks, an Ataxia telangiectasia mutated (ATM)-dependent DNA-damage response, an increased expression of the Interferon regulatory factor 5 (IRF5) and the release of proinflammatory cytokines from targeted macrophages, thus directing their proinflammatory reprogramming. This process is associated with the activating phosphorylation of the Adenosine Monophosphate (AMP) activated protein kinase on threonine 172 (AMPKT172*) and the fragmentation of mitochondria. Furthermore, we demonstrate that the inactivation of AMPK reduces the mitochondrial fragmentation and the proinflammatory reprogramming of macrophages detected in response to AGuIX and their combination with IR. These results reveal that the AMPK-dependent regulation of mitochondrial fragmentation plays a central role during the proinflammatory reprogramming of macrophages. Accordingly, a positive correlation between AMPKT172* and proinflammatory activation of TAMs is detected following IR+AGuIX combination in syngeneic mouse model of colorectal cancer. ConclusionsAltogether, our results identify a novel signaling pathway elicited by AGuIX and their combined treatment with IR, that targets macrophage polarization, skews macrophage functions toward the proinflammatory phenotype and may enhance the effectiveness of radiotherapy.

immunology↗

bioRxiv2022

Retinotopic organization of feedback projections in primate early visual cortex: implications for active vision

Feedback connections play a major role in many theories of brain function. Previous studies of feedback connections to early visual areas have mainly concentrated on the representation of central visual fields. Here, injections of tracers at different eccentricities in areas V1 and V2 revealed retinotopically organized feedback. Peripheral injections revealed projections from 15 areas that are not labeled by central injections. Connection strengths for the majority of projections vary significantly with eccentricity in a systematic fashion with respect to distance and origin; whereas projections to central and upper visual fields are significantly stronger from ventral stream areas, peripheral and lower field projections are stronger from the dorsal stream. Non-invasive functional connectivity suggests a similar anatomical organization in humans. These features are discussed with respect to the cognitive and perceptual roles of these feedback pathways.

neuroscience↗

bioRxiv2020

Neural stem cells restore motor and cognitive function in a macaque model of Parkinson's disease

Parkinsons disease (PD) evolves over an extended and variable period in humans; several years prior to the onset of classical motor symptoms, cognitive deficits as well as sleep and biological rhythm disorders develop and worsen with disease progression, significantly impacting the quality of life of patients. The gold standard MPTP macaque model of PD recapitulates the progression of motor and non-motor symptoms over contracted periods of time. Here, this multidisciplinary and multiparametric study follows, in five animals, the steady progression of motor and non-motor symptoms and describes their reversal following bilateral grafts of neural precursors in diverse functional domains of the basal ganglia. Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration into the host environment as well as with in-vivo levels of striatal dopaminergic innervation and function. Given inter-individuality of disease progression and recovery the present study underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation and provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian non-human primates. One Sentence SummaryEmpirical evidence that cell therapy efficiently reverts cognitive and clinical motor symptoms in the non-human primate model of Parkinsons disease.

neuroscience↗

bioRxiv2019

Bisphenol A promotes stress granule assembly and modulates the integrated stress response

Bisphenol-A (BPA) is a ubiquitous precursor of polycarbonate plastics that is found in the blood and serum of >92% of Americans. While BPA has been well documented to act as a weak estrogen receptor (ER) agonist, its effects on cellular stress are unclear. Here, we demonstrate that high-dose BPA causes stress granules (SGs) in human cells. A common estrogen derivative, {beta}-estradiol, does not trigger SGs, indicating the mechanism of SG induction is not via the ER pathway. We also tested other structurally related environmental contaminants including the common BPA substitutes BPS and BPF, the industrial chemical 4-nonylphenol (4-NP) and structurally related compounds 4-EP and 4-VP, and the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D). The variable results from these related compounds suggest that structural homology is not a reliable predictor of the capacity of a compound to cause SGs. Also, we demonstrate that BPA acts primarily through the PERK pathway to generate canonical SGs. Finally, we show that chronic exposure to a low physiologically relevant dose of BPA disrupts SG assembly by inhibiting SGs upon additional acute stress. Our work identifies additional effects of BPA beyond endocrine disruption that may have consequences for human health.

cell biology↗