Biology subjects

Miellet, S.

Publications and source records attributed to Miellet, S..

6 recordsLinked to original sources

bioRxiv2026

Naturalistic face-directed attention predicts face recognition ability

Recognising people precedes and informs most social interactions, yet it is not clear why individuals differ so markedly in face recognition ability. Exposure-based accounts propose that it is shaped by visual experience with faces, known as 'face diet', but most prior work treats exposure as passively acquired, thereby masking the active and dynamic nature of visual attention in natural settings. Here we examined whether spontaneous attention to faces in everyday environments predicts face recognition ability. Eighty participants wore mobile eye-tracking glasses while walking through a busy university campus and during a face-to-face interaction, before completing standard measures of face recognition ability. Fixations directed to faces showed stable individual differences in both settings. People who looked more at faces scored higher on our composite measure of face recognition ability, and gaze in the two settings predicted ability independently, together accounting for 22% of its variance. These findings suggest that differences in how people actively sample visual information from their environments may be an overlooked source of variance in perceptual expertise.

animal behavior and cognition↗

bioRxiv2026

Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis

Friedreich ataxia (FRDA) is a progressive multisystem neurodegenerative disease mostly caused by a homozygous GAA repeat expansion in the FXN gene, leading to deficiency of the protein frataxin. Despite ubiquitous frataxin expression, FRDA pathology is tissue-specific, disproportionately affecting dorsal root ganglia sensory neurons, dentate nuclei of the cerebellum, corticospinal tracts and cardiomyocytes. The molecular basis for this selective vulnerability remains unresolved, suggesting that cell-type specific responses to frataxin deficiency shape disease susceptibility. This incomplete understanding is compounded by the lack of molecular biomarkers that capture FRDA biology beyond frataxin deficiency, thereby limiting therapeutic development and evaluation. Here, we integrated all available human bulk RNA-seq datasets in FRDA (23 datasets across 10 cell types), spanning disease-related (cardiomyocytes, sensory neurons) and relatively FRDA-spared cell types (fibroblasts, lymphoblastoid cells) under a unified analytical framework to identify transcriptional dysregulation underlying selective vulnerability and candidate biomarkers. Meta-analysis revealed recurrent transcriptional perturbations beyond FXN, involving long non-coding RNAs, translational control and cytoskeletal organisation. While shared transcriptional themes were observed, the specific biological programmes engaged were strongly cell-type dependent. The top candidate biomarkers, MYH14, MEG9, and MEG8 showed preferential upregulation in disease-relevant cell types including sensory neurons and cardiomyocytes, supporting their potential relevance to selective vulnerability. Therapeutic responsiveness to these candidates were assessed across RNA-seq datasets from FRDA models exposed to diverse therapeutic strategies, including epigenetic modulation and FXN-targeting approaches, revealing that transcriptional alterations in FRDA are pharmacologically modifiable. To facilitate transparent exploration and reuse of these findings, we developed an interactive FRDA Transcriptomic Atlas, providing a community-accessible resource for investigating gene and pathway-level dysregulation across FRDA studies: https://marniemaddock.github.io/FRDATranscriptomicAtlas/. Together, these findings implicate cell type specific transcriptional programs as potential drivers of selective vulnerability and establish a framework for prioritising biomarkers in FRDA. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/712785v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@26138org.highwire.dtl.DTLVardef@3cbc27org.highwire.dtl.DTLVardef@164dbf5org.highwire.dtl.DTLVardef@a4b59d_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

REST and RCOR genes display distinct expression profiles in neurons and astrocytes using 2D and 3D human pluripotent stem cell models

Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor involved in neurodevelopment and neuroprotection. REST forms a complex with the REST corepressors, CoREST1, CoREST2, or CoREST3 (encoded by RCOR1, RCOR2, and RCOR3, respectively). Emerging evidence suggests that the CoREST family can target unique genes independently of REST, in various neural and glial cell types during different developmental stages. However, there is limited knowledge regarding the expression and function of the CoREST family in human neurodevelopment. To address this gap, we employed 2D and 3D human pluripotent stem cell (hPSC) models to investigate REST and RCOR gene expression levels. Our study revealed a significant increase in RCOR3 expression in glutamatergic cortical and GABAergic ventral forebrain neurons, as well as mature functional NGN2-induced neurons. Additionally, a simplified astrocyte transdifferentiation protocol resulted in a significant decrease in RCOR2 expression following differentiation. REST expression was notably reduced in mature neurons and cerebral organoids, along with RCOR2 in the latter. In summary, our findings provide the first insights into the cell-type-specific expression patterns of RCOR genes in human neuronal and glial differentiation. Specifically, RCOR3 expression increases in neurons, while RCOR2 levels decrease in astrocytes. The dynamic expression patterns of REST and RCOR genes during hPSC neuronal and glial differentiation underscore the potential distinct roles played by REST and CoREST proteins in regulating the development of these cell types in humans. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/584254v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@7be30borg.highwire.dtl.DTLVardef@1771388org.highwire.dtl.DTLVardef@a376aforg.highwire.dtl.DTLVardef@1c4dc83_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIREST and RCOR genes display cell-type specific expression patterns in neural cells C_LIO_LIRCOR3 (encodes CoREST3) is upregulated during neuronal and astrocyte differentiation C_LIO_LIRCOR2 (encodes CoREST2) is downregulated during differentiation of astrocytes C_LIO_LIEvidence of potential cell-type specific functions of the CoREST family C_LI

neuroscience↗

bioRxiv2023

Parsing the effect of co-culture with brain organoids on Diffuse Intrinsic Pontine Glioma (DIPG) using quantitative proteomics

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly brain cancers in children for which there is currently no effective treatment. This can partly be attributed to preclinical models that lack essential elements of the in vivo tissue environment, resulting in treatments that appear promising preclinically, but fail to result in effective cures. Recently developed co-culture models combining stem cell-derived brain organoids with brain cancer cells provide tissue dimensionality and a human-relevant tissue-like microenvironment. As these models are technically challenging and time consuming it is imperative to establish whether interaction with the organoid influences DIPG biology and thus warrants their use. To address this question, we cultured DIPG cells with cortical organoids. We created "mosaic" co-cultures enriched for tumour cell-neuronal cell interactions versus "assembloid" co-cultures enriched for tumour cell-tumour cell interactions. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) was used to analyse the proteomes of DIPG fractions isolated by flow-assisted cell sorting. Control proteomes from DIPG spheroids were compared with DIPG cells isolated from mosaic and assembloid co-cultures. This revealed that tumour cell adhesion was reduced, and DNA synthesis and replication were increased, in DIPG cells under either co-culture condition. By contrast, the mosaic co-culture was associated with pathways implicated in dendrite growth. We propose that co-culture with brain organoids is a valuable tool to parse the contribution of the brain microenvironment to DIPG tumour biology.

cancer biology↗

bioRxiv2019

In pursuit of visual attention: SSVEP frequency-tagging moving targets

Previous research has shown that visual attention does not always exactly follow gaze direction, leading to the concepts of overt and covert attention. However, it is not yet clear how such covert shifts of visual attention to peripheral regions impact the processing of the targets we directly foveate as they move in our visual field. The current study utilised the co-registration of eye-position and EEG recordings while participants tracked moving targets that were embedded with a 30 Hz frequency tag in a Steady State Visually Evoked Potentials (SSVEP) paradigm. When the task required attention to be divided between the moving target (overt attention) and a peripheral region where a second target might appear (covert attention), the SSVEPs elicited by the tracked target at the 30 Hz frequency band were significantly lower than when participants did not have to covertly monitor for a second target. Our findings suggest that neural responses of overt attention are reduced when attention is divided between covert and overt areas. This neural evidence is in line with theoretical accounts describing attention as a pool of finite resources, such as the perceptual load theory. Altogether, these results have practical implications for many real-world situations where covert shifts of attention may reduce visual processing of objects even when they are directly being tracked with the eyes.

neuroscience↗

bioRxiv2019

Multilevel regulation of the glass locus during Drosophila eye development

Development of eye tissue is initiated by a conserved set of transcripton factors termed retinal determination network (RDN). In the fruit fly Drosophila melanogaster, the zinc-finger transcription factor Glass acts directly downstream of the RDN to control idendity of photoreceptor as well as non-photoreceptors cells. Tight control of spatial and temporal gene expression is a critical feature during development, cell-fate determination as well as maintainance of differentiated tissues. The molecular mechanisms that control expression of glass, however remain largely unknown. We here identify complex regulatory mechanisms controlling expression of the glass locus. All information to recapitulate glass expression are contained in a compact 5.2 kb cis-acting genomic element by combining different cell-type specific and general enhancers with repressor elements. Moreover, the immature RNA of the locus contains an alterantive small open reading frame (smORF) upstream of the actual glass translation start, resulting in a small peptide instead of the three possible glass protein isoforms. CRISPR/Cas9-based mutagenesis shows that the smORF is not required for the formation of functioning photoreceptors, but to attenuate effects of glass misexpression. Furthermore, editing the genome to generate glass loci eliminating either one or two isoforms shows that only one of the three proteins is critical for formation of functioning photoreceptors, while removing the two other isoforms did not cause defects in developmental or photoreceptor function. Our results show that eye development and function is surprisingly robust and appears buffered to targeted manipulations of critical features of the glass transcript, suggesting a strong selection pressure to allow the formation of a functioning eye.

developmental biology↗