Biology subjects

Droin, C.

Publications and source records attributed to Droin, C..

4 recordsLinked to original sources

bioRxiv2025

The lipidomic architecture of the mouse brain

Lipids are fundamental components of the brain, crucial for synaptic transmission and signal propagation. Altered brain lipid composition is associated with common and rare neuropathologies, yet, the spatial organization of the mammalian brain lipidome remains insufficiently characterized compared to other modalities1-8. Here, we mapped the membrane lipid architecture of the adult mouse brain at micrometric scale, across sexes, and during pregnancy. This Lipid Brain Atlas reveals that lipids define a fine-grained biochemical structure that aligns with functional anatomy. Membrane lipid spatial heterogeneity clusters into territories, which we termed lipizones. Lipizones partially mirror cell type territories, but also capture distal axon terminals. Through lipizones, (i) we reveal the organizing principles of the gray matter lipidome, related to connectivity and cytoarchitecture; (ii) we discover a new axis of oligodendrocyte heterogeneity in the white matter; (iii) and we find biochemical zonation in the choroid plexus and in the ventricular walls. We show that this lipidomic architecture can adapt to changing physiological needs. In the brain of pregnant females, the white matter is metabolically activated and the outer cortex is reorganized. These results are a foundational resource (https://lbae-v2.epfl.ch/), poised to reshape our understanding of lipids in brain development, physiology, and pathology.

systems biology↗

bioRxiv2024

Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations

Across a range of biological processes, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. Single-cell RNA-sequencing (scRNA-seq) only measures temporal snapshots of gene expression. However, information on the underlying low-dimensional dynamics can be extracted using RNA velocity, which models unspliced and spliced RNA abundances to estimate the rate of change of gene expression. Available RNA velocity algorithms can be fragile and rely on heuristics that lack statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. Here, we develop a generative model of RNA velocity and a Bayesian inference approach that solves these problems. Our model couples velocity field and manifold estimation in a reformulated, unified framework, so as to coherently identify the parameters of an autonomous dynamical system. Focusing on the cell cycle, we implemented VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validated using live-imaging its ability to infer actual cell cycle periods. We benchmarked RNA velocity inference with sensitivity analyses and demonstrated one- and multiple-sample testing. We also conducted Markov chain Monte Carlo inference on the model, uncovering key relationships between gene-specific kinetics and our gene-independent velocity estimate. Finally, we applied VeloCycle to in vivo samples and in vitro genome-wide Perturb-seq, revealing regionally-defined proliferation modes in neural progenitors and the effect of gene knockdowns on cell cycle speed. Ultimately, VeloCycle expands the scRNA-seq analysis toolkit with a modular and statistically rigorous RNA velocity inference framework.

systems biology↗

bioRxiv2020

Space-time logic of liver gene expression at sublobular scale

The mammalian liver performs key physiological functions for maintaining energy and metabolic homeostasis. Liver tissue is both spatially structured and temporally orchestrated. Hepatocytes operate in repeating anatomical units termed lobules and different lobule zones perform distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. Liver zonation was previously analyzed as a static phenomenon and liver chronobiology at the tissue level. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Categorizing mRNA expression profiles using mixed-effect models and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, most of them showing multiplicative space-time effects. Such dually regulated genes cover key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also genes not previously associated with liver zonation such as chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our comprehensive scRNA-seq analysis revealed how liver function is compartmentalized spatio-temporally at the sub-lobular scale.

systems biology↗

bioRxiv2019

Low-dimensional Dynamics of Two Coupled Biological Oscillators

The circadian clock and the cell cycle are two biological oscillatory processes that coexist within individual cells. These two oscillators were found to interact, which can lead to their synchronization. Here, we develop a method to infer their coupling and non-linear dynamics from thousands of mouse and human single-cell microscopy traces. This coupling predicts multiple phase-locked states showing different degrees of robustness against molecular fluctuations inherent to cellular scale biological oscillators. Moreover, the phase-locked states were temperature-independent and evolutionarily conserved from mouse to human, hinting at a common underlying dynamical mechanism. Finally, we detected a signature of the coupled dynamics in a physiological context, where tissues with different proliferation states exhibited shifted circadian clock phases.

systems biology↗