Biology subjects

Cattin, A.-L.

Publications and source records attributed to Cattin, A.-L..

4 recordsLinked to original sources

bioRxiv2026

Quantitative spatial connectomics of liver reveals a partially exposed sympathetic network that integrates multiple cell types across the portal tract

Peripheral tissues are innervated by sparse axonal networks that regulate homeostasis, regeneration and disease, yet their three-dimensional architecture and cellular targets remain largely unknown. Here, we present an EM workflow for quantitative 3D spatial connectomics to define these networks. We identify the mouse liver connectome as a meshwork, rather than a tree-like structure, of mainly sympathetic axons, in which partial Schwann cell coverage is associated with exposed varicosities along the length of individual axons with large regions of the network devoid of glial coverage. Axon tracing identified axonal terminals throughout the network, but the vast majority of cellular contacts involved exposed 'en passant' varicosities. While both terminals and varicosities innervated the vasculature, most synaptic-like contacts involved hepatocytes, fibroblasts, macrophages, and the stem-cell niche, with all individual axons contacting different cell types along their length, highlighting the network nature of liver innervation, the potential for co-ordinating tissue function and demonstrating the power of this approach for decoding connectivity in peripheral tissues.

neuroscience↗

bioRxiv2026

Distinct functions of PBRM1 and BAP1 reconcile the course of kidney cancer evolution and disease progression

Clear cell renal cell carcinoma (ccRCC) progresses along two predominant evolutionary trajectories, defined by PBRM1 ([~]40%) or BAP1 ([~]15%) mutations on a VHL-inactivated background. They have distinct patterns of evolutionary tempo and mode, and vastly different clinical outcomes, yet the underlying genotype-specific molecular phenotypic programmes are unknown. We established a patient-derived preclinical model biobank that captures the genetic diversity of ccRCC. Through integrative analyses of preclinical models and tumour bulk and single cell profiling, we identified transcriptional and epigenetic changes specific to PBRM1- and BAP1-driven ccRCC. Modelling PBRM1 loss in vitro demonstrates that it reinforces renal lineage identity and maintains progenitor-like cell state. In contrast, BAP1 loss drives inflammatory signalling and chromosomal instability. These insights reconcile the distinct evolutionary modes (branched versus punctuated), tempo (slow versus fast) and clinical outcomes associated with PBRM1 and BAP1 mutations, respectively, establishing a framework for patient stratification and genotype-directed therapeutic development.

cancer biology↗

bioRxiv2025

Chromosome-Specific Aneuploidy Engineering via dCas9-Induced Centromeric Chromatin Relaxation

Aneuploidy, the gain or loss of chromosomes, is prevalent in both normal and disease conditions, however, experimental approaches to engineer and study aneuploidy remain limited, leaving its functional significance under-characterized. Here, we present CRISPR-Taiji (CRISPRt), an efficient method for inducing chromosome-specific mis-segregation and aneuploidy generation across all 24 human chromosomes via dead Cas9 (dCas9)-induced centromeric chromatin relaxation. Using CRISPRt with scRNA-seq, we generated the first comprehensive transcriptomic alteration landscape of nearly all autosomal aneuploidies at chromosome-arm resolution. This genotype-phenotype map provides causal evidence linking recurrent aneuploidies in clear cell renal cell carcinoma (ccRCC) to molecular and clinical phenotypes observed in patient tumors. Notably, chromosome 3(p) loss, the ccRCC initiating event, specifically drives strong interferon signaling activation, offering novel insights into ccRCC tumorigenesis and immune modulation. Overall, we establish CRISPRt as a simple, efficient and scalable approach for chromosome-specific aneuploidy engineering and characterization in preclinical models to advance aneuploidy research across diverse biological contexts.

genomics↗

bioRxiv2019

N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration

Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.

molecular biology↗