Biology subjects

Schede, H. H.

Publications and source records attributed to Schede, H. H..

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

Unified Mass Imaging Maps the Lipidome of Vertebrate Development

Embryo development entails the formation of anatomical structures with distinct biochemical compositions. Compared with the wealth of knowledge on gene regulation, our understanding of metabolic programs operating during embryogenesis is limited. Mass spectrometry imaging (MSI) has the potential to map the distribution of metabolites across embryo development. Here, we established an analytical framework for the joint analysis of large MSI datasets that allows for the construction of multi-dimensional metabolomic atlases. Employing this framework, we mapped the 4D distribution of over a hundred lipids at quasi-single-cell resolution in Danio rerio embryos. We discovered metabolic trajectories that unfold in concert with morphogenesis and revealed spatially organized biochemical coordination overlooked by bulk measurements. Interestingly, lipid mapping revealed unexpected distributions of sphingolipid and triglyceride species, suggesting their involvement in pattern establishment and organ development. Our approach empowers a new generation of whole-organism metabolomic atlases and enables the discovery of spatially organized metabolic circuits.

systems biology↗

bioRxiv2022

Organization and regulation of nuclear condensates by gene activity

Condensation by phase separation has recently emerged as a mechanism underlying many nuclear compartments essential for cellular functions. Nuclear condensates enrich nucleic acids and proteins, localize to specific genomic regions, and often promote gene expression. How diverse properties characteristic of nuclear condensates are shaped by genome organization and activity is poorly understood. Here, we develop a physics-based model to interrogate this interplay between condensation, active transcription, and genome organization. We show that spatial clustering of active genes enables precise localization and de novo nucleation of condensates. We find that strong clustering and activity drives aspherical condensate morphologies. Condensates flow towards distant gene clusters and competition between multiple clusters lead to stretched morphologies and activity-dependent repositioning. Overall, our model predicts and recapitulates morphological and dynamical features of diverse nuclear condensates and offers a unified mechanistic framework to study the interplay between non-equilibrium processes, genome structure, and multicomponent condensates in cell biology.

biophysics↗

bioRxiv2020

Spatial tissue profiling by imaging-free molecular tomography

Genomics techniques are currently being adapted to provide spatially resolved omics profiling. However, the adaptation of each new method typically requires the setup of specific detection strategies or specialized instrumentation. A generic approach to spatially resolve different types of high throughput data is missing. Here, we describe an imaging-free framework to localize high throughput readouts within a tissue by combining compressive sampling and image reconstruction. We implemented this framework to transform a low-input RNA sequencing protocol into an imaging-free spatial transcriptomics technique (STRP-seq) and validated this method with a transcriptome profiling of the murine brain. To verify the broad applicability of STRP-seq, we applied the technique on the brain of the Australian bearded dragon Pogona vitticeps. Our results reveal the molecular anatomy of the telencephalon of this lizard, providing evidence for a marked regionalization of the reptilian pallium and subpallium. Overall, the proposed framework constitutes a new approach that allows upgrading in a generic fashion conventional genomic assays to spatially resolved techniques.

genomics↗