Biology subjects

Patthey, C.

Publications and source records attributed to Patthey, C..

4 recordsLinked to original sources

bioRxiv2025

Enrichment of neural crest cells by antibody labelling and flow cytometry for single-cell transcriptomics in a lizard

Neural crest cells (NCCs) are a key component of the vertebrate body plan and contribute to a variety of different traits. However, their dynamic migratory behavior and spatiotemporal heterogeneity in the developing embryo pose significant challenges for their identification and isolation. Consequently, most studies of NCCs have been confined to model organisms with established transgenic tools. To overcome this limitation, we present a novel approach that combines antibody labelling with fluorescence activated cell sorting to enrich for NCCs and we demonstrate the approach in the common wall lizard (Podarcis muralis). Through microscopy, reverse transcription quantitative polymerase chain reaction and single-cell RNA sequencing, we show that the method enriches for NCCs as efficiently as methods relying on transgenic animals. Using this technique, we successfully characterise transcriptional profiles of NCCs in wall lizard embryos. We anticipate that this method can be applied to a wide range of vertebrates that lack transgenic tools, enabling deeper insights into the roles that neural crest cells are playing in developmental and evolution.

developmental biology↗

bioRxiv2022

High throughput screen in a co-culture model to uncover therapeutic strategies to potentiate the cancer-inhibiting properties of the tumor-stroma in pancreatic cancer

Pancreatic stellate cells (PSCs) differentiate into multiple subtypes of cancer associated fibroblasts (CAFs) that modulate disease progression in pancreatic ductal adenocarcinoma (PDAC). CAF subtypes demonstrate functional heterogeneity in tumor development, with conflicting consequences for disease progression. Here, we show that myofibroblastic CAFs (myCAFs), but not inflammatory CAFs (iCAFs), can act to restrain tumor cell growth in an in vitro PDAC model of tumor organoids co-cultured with PSCs. Inhibiting myCAF formation by TGF-{beta} pathway inhibition improved tumor organoid growth, indicating that manipulating the balance of CAF subtypes may be exploited as a therapeutic approach. We therefore conducted a high throughput screen of approximately 36,000 compounds on the co-culture model to find novel compounds to inhibit PDAC tumor cell growth via CAF manipulation. We identify a new role for GNF-5, a known Abelson tyrosine kinase (Abl) inhibitor, in the context of PDAC as a compound that inhibits tumor cell growth in co-culture; an effect that was accompanied by an induction of the myCAF phenotype around tumor organoids. This highlights the therapeutic potential of novel therapies targeting specific CAF subtypes in PDAC.

cancer biology↗

bioRxiv2020

Hmx gene conservation identifies the evolutionary origin of vertebrate cranial ganglia

The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle1. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia (CSG) which develop from cranial placodes; however understanding the evolutionary origin of placodes and CSGs is hampered by the gulf between living lineages and difficulty in assigning homology between cell types and structures. Here we use the Hmx gene family to address this question. We show Hmx is a constitutive component of vertebrate CSG development and that Hmx in the tunicate Ciona is able to drive the differentiation program of Bipolar Tail Neurons (BTNs), cells previously thought neural crest homologs2,3. Using Ciona and lamprey transgenesis we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx in the stem-vertebrate lineage. Strikingly, we also show robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and confirm BTNs as CSG homologs. Our analysis also identifies derived evolutionary changes, including a genetic basis for secondary simplicity in Ciona and unique regulatory complexity in vertebrates.

evolutionary biology↗

bioRxiv2018

A Notch-regulated proliferative stem cell zone in the developing spinal cord is an ancestral vertebrate trait

Vertebrates have evolved the most sophisticated nervous systems we know. These differ from the nervous systems of invertebrates in several ways, including the evolution of new cell types, and the emergence and elaboration of patterning mechanisms to organise cells in time and space. Vertebrates also generally have many more cells in their central nervous systems than invertebrates, and an increase in neural cell number may have contributed to the sophisticated anatomy of the brain and spinal cord. Here we study how increased cell number evolved in the vertebrate central nervous system, investigating the regulation of cell proliferation in lampreys as basally-diverging vertebrate, and focusing on the spinal cord because of its relatively simple anatomy. Markers of proliferating cells show that a medial proliferative progenitor zone is found throughout the lamprey spinal cord. We show that inhibition of Notch signalling disrupts the maintenance of this proliferative zone. When Notch signalling is blocked progenitor cells differentiate precociously, the proliferative medial zone is lost, and differentiation markers activate throughout the medial-lateral axis of the spinal cord. Comparison to other chordates suggests that the emergence of a persistent Notch-regulated proliferative progenitor zone in the medial spinal cord of vertebrate ancestors was a critical step for the evolution of the vertebrate spinal cord and its complexity.\n\nSummary statementVertebrates develop nervous systems with numerous cells. Study of cell proliferation in the lamprey nervous system links this to a medial proliferation zone regulated by Notch signalling, a vertebrate innovation.

evolutionary biology↗