Biology subjects

Chaigne, A.

Publications and source records attributed to Chaigne, A..

4 recordsLinked to original sources

bioRxiv2026

Wnt signalling controls abscission dynamics in mouse embryonic stem cells

Cell division is a crucial process that ensures proper development of multicellular organisms. Cell division ends in abscission, a process in which the intercellular bridge between two sister cells is cut. Although abscission usually happens shortly after chromosome segregation, abscission is severely delayed in mouse embryos and embryonic stem cells (mESC). The regulation of the duration of abscission influences cell fate transitions but how cell state and abscission dynamics crosstalk remains unknown. Here, we show that a key pluripotency pathway, the Wnt signalling pathway, controls abscission dynamics. Upon deactivation of Wnt signalling in naive mESCs, abscission becomes faster. Wnt signalling regulates abscission dynamics in mESCs through two mechanisms. First, Wnt signalling keeps the amount of Aurora B high at the intercellular bridge, probably by preventing Aurora B degradation. In turn, high Aurora B activity at the bridge delays bridge abscission. Second, a key component of Wnt signalling, the kinase GSK-3{beta} localizes at the intercellular bridge with microtubules and their associated proteins (MAPs). In pluripotent cells, inactivation of GSK-3{beta} leads to an increase of stable microtubules at the bridge stable which causes delayed abscission. Crucially, inhibition of GSK-3{beta} after cells have exited naive pluripotency accelerates abscission, demonstrating that cell state influences the output of the abscission signalling pathway. The permissive function of canonical Wnt on cell state is thought to be mediated by reinforcement of existing pluripotency network; altogether, our work shows that non-canonical Wnt is also context dependent.

cell biology↗

bioRxiv2024

Aurora B controls microtubule stability to regulate abscission dynamics in stem cells

Abscission is the last step of cell division leading to the complete separation of the two sister cells and consists of the cutting of a cytoplasmic bridge. Abscission is mediated by the ESCRT membrane remodeling machinery which also triggers the severing of a thick bundle of microtubules that needs to be cleared prior to abscission. Here, we show that rather than being passive actors in abscission, microtubules control abscission speed. Using mouse embryonic stem cells, which transition from slow to fast abscission during exit from naive pluripotency, we investigate the molecular mechanism for the regulation of abscission dynamics and identify a feedback loop between the activity of Aurora B and microtubule stability. We demonstrate that naive stem cells maintain high Aurora B activity after cytokinesis. This high Aurora B activity leads to transient microtubule stabilization that delays abscission. In turn, stable microtubules promote the activity of Aurora B. When cells exit naive pluripotency, a decrease in Wnt signaling leads to a decrease in the activity of Aurora B, less stable microtubules, and a faster abscission. Overall, our data demonstrate that Aurora B-dependent microtubule stability controls abscission dynamics.

cell biology↗

bioRxiv2023

Active mesh and neural network pipeline for cell aggregate segmentation

Segmenting cells within cellular aggregates in 3D is a growing challenge in cell biology, due to improvements in capacity and accuracy of microscopy techniques. Here we describe a pipeline to segment images of cell aggregates in 3D. The pipeline combines neural network segmentations with active meshes. We apply our segmentation method to cultured mouse mammary duct organoids imaged over 24 hours with oblique plane microscopy, a high-throughput light-sheet fluorescence microscopy technique. We show that our method can also be applied to images of mouse embryonic stem cells imaged with a spinning disc microscope. We segment individual cells based on nuclei and cell membrane fluorescent markers, and track cells over time. We describe metrics to quantify the quality of the automated segmentation. Our segmentation pipeline involves a Fiji plugin which implement active meshes deformation and allows a user to create training data, automatically obtain segmentation meshes from original image data or neural network prediction, and manually curate segmentation data to identify and correct mistakes. Our active meshes-based approach facilitates segmentation postprocessing, correction, and integration with neural network prediction. Statement of significanceIn vitro culture of organ-like structures derived from stem cells, so-called organoids, allows to image tissue morphogenetic processes with high temporal and spatial resolution. Three-dimensional segmentation of cell shape in timelapse movies of these developing organoids is however a significant challenge. In this work, we propose an image analysis pipeline for cell aggregates that combines deep learning with active contour segmentations. This combination offers a flexible and efficient way to segment three-dimensional cell images, which we illustrate with by segmenting datasets of growing mammary gland organoids and mouse embryonic stem cells.

bioinformatics↗

bioRxiv2019

Abscission couples cell division to embryonic stem cell fate

Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cells, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs exit from naive pluripotency. Altogether, our data indicate that a switch in the division machinery leading to faster abscission is crucial for pluripotency exit. Our study identifies abscission as a key step coupling cell division to fate transitions.

cell biology↗