Biology subjects

Adle-Biassette, H.

Publications and source records attributed to Adle-Biassette, H..

3 recordsLinked to original sources

bioRxiv2025

Multimodal imaging of human fetal brain development at the mesoscopic scale using 11.7 T ex vivo MRI

We present the first release of p-HCP (Prenatal Human Connectome Patterns), an imaging dataset of human fetal brain development covering the second half of gestation. This dataset was acquired ex vivo using magnetic resonance imaging (MRI) at ultra high field (11.7 teslas), and includes whole-hemisphere T2-weighted images at 100 {micro}m isotropic resolution, quantitative relaxometry (T1, T2, and [Formula]), and high angular resolution diffusion-weighted images for multiple b-values at 200 {micro}m. Brains larger than the workspace of the small-bore scanner were sectioned into blocks, acquired blockwise, and digitally reconstructed using a dedicated semi-automatic method. This initial data release includes three gestational ages (18, 27, and 31 post-conceptional weeks) with a complete set of anatomical images, relaxometry maps, and diffusion-based microstructure measurements. This dataset offers new opportunities to investigate neurodevelopmental processes that have not yet been explored with full three-dimensional coverage at this resolution by MRI, and may serve as a multimodal mesoscopic reference template for the fetal brain.

neuroscience↗

bioRxiv2025

A Catalytically Inactive Protein Kinase C alpha Mutation Drives Chordoid Glioma by Pathway Rewiring

Abstract SummaryChordoid glioma (ChG) is a rare, low-grade brain tumor characterized by a novel recurrent point mutation, D463H, in the kinase domain of protein kinase C alpha (PKC). The mutation is invariably an Asp to His substitution, suggesting it endows a unique function beyond catalytic inactivation associated with other cancer-associated PKC mutations. Here we use in vitro and in cellulo activity assays to show that PKCD463H is catalytically inactive, functions as a dominant-negative mutant to suppress endogenous PKC and uniquely rewires the cellular interactome. Specifically, phosphoproteomic, proximity labeling, and co-immunoprecipitation mass-spectrometry data from cells overexpressing PKCD463H identify altered phosphorylation of substrates and binding to multiple proteins involved in cell-cell junctions compared to WT enzyme. Lastly, single nuclei RNAseq reveals that ChG derives from specialized tanycytes. Our data suggest that this disease-defining, fully penetrant mutation promotes neomorphic non-catalytic scaffolding to impair cell junction function.

molecular biology↗

bioRxiv2019

Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex

Variation in gene expression underlies neurotypical development, while genomic variants contribute to neuropsychiatric disorders. BrainVar is a unique resource of paired whole-genome sequencing and bulk-tissue RNA-sequencing from the human dorsolateral prefrontal cortex of 176 neurotypical individuals across prenatal and postnatal development, providing the opportunity to assay genomic and transcriptomic variation in tandem. Leveraging this resource, we identified rare premature stop codons with commensurate reduced and allele-specific expression of corresponding genes, and common variants that alter gene expression (expression quantitative trait loci, eQTLs). Categorizing eQTLs by prenatal and postnatal effect, genes affected by temporally-specific eQTLs, compared to constitutive eQTLs, are enriched for haploinsufficiency, protein-protein interactions, and neuropsychiatric disorder risk loci. Expression levels of over 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell type specific genes and neuropsychiatric disorder loci, underscoring the importance of cataloguing developmental trajectories in understanding cortical physiology and pathology.\n\nHighlightsO_LIWhole-genome and RNA-sequencing across human prefrontal cortex development in BrainVar\nC_LIO_LIGene-specific developmental trajectories characterize the late-fetal transition\nC_LIO_LIIdentification of constitutive, prenatal-specific, postnatal-specific, and rare eQTLs\nC_LIO_LIIntegrated analysis reveals genetic and developmental influences on CNS traits and disorders\nC_LI

neuroscience↗