Biology subjects

Guilliams, M.

Publications and source records attributed to Guilliams, M..

7 recordsLinked to original sources

bioRxiv2026

Modeling spheroid assembly dynamics and mechanical stress generation in magnetic-based biofabrication

Magnetic biofabrication enables rapid assembly of multicellular spheroids but still lacks a basis for predictive control over structure and mechanical environment. Here, we combine experiments and an individual spheroid-based model to study magnetic assembly of periosteum-derived spheroids. Spheroids are treated as discrete particles interacting through magnetic forces, contact mechanics, and interfacial friction, with parameters obtained from independent measurements. This model quantitatively captures assembly dynamics arising from magnetic force patterns and viscous drag with the well surface. The spatial distribution of magnetic forces, determined by magnet geometry and positioning, predicts the size and morphology of magnetic assembloids, including disk- and ring-like structures. Magnetic assembly further generates heterogeneous compressive stresses that depend on magnet geometry and spheroid number. Radial stresses arise collectively through inter-spheroid interactions, whereas vertical stresses are mainly determined by magnetic loading of individual spheroids. These results establish a minimal physical framework for magnetic biofabrication and provide a basis for predictive control of both tissue structure and mechanical microenvironment.

bioengineering↗

bioRxiv2024

SPArrOW: a flexible, interactive and scalable pipeline for spatial transcriptomics analysis

Current spatial transcriptomics technologies are increasingly able to measure large gene panels at subcellular resolution, but a major bottleneck in this rapidly advancing field is the computational analysis and interpretation of the data. To bridge this gap, here we present SPArrOW, a flexible, modular and scalable pipeline for processing spatial transcriptomics data. SPArrOW improves cell segmentation and leads to better overall data quality, resulting in more accurate cell annotations at the single-cell level. Furthermore, it provides the users with numerous visual quality checks that are crucial for the correct interpretation of the data, offering users more control in processing their data. Our workflow is designed to accommodate the various available spatial transcriptomics platforms. Finally, SPArrOW offers interactive visualization and data exploration, enabling sample-specific pipeline optimization by various tuneable parameters and an efficient comparison of different staining and gene allocation strategies.

bioinformatics↗

bioRxiv2023

CD163 and Tim-4 identify resident intestinal macrophages across sub-tissular regions that are spatially regulated by TGF-β

In bodily organs, macrophages are localised in poorly understood tissular and sub-tissular niches associated with defined macrophage ontogeny and activity. In the intestine, a paradigm is emerging that long-lived macrophages are dominantly present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria beneath the epithelial barrier. Whether longevity is restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on long-lived macrophage functionality and niche occupancy is unknown. We generated sc-RNA-Seq data from wild-type and Ccr2-/- mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal niches and identified CD163 as a useful marker to distinguish submucosal/muscularis (S/M) from lamina propria (LP) macrophages. Challenging the emerging paradigm, long-lived macrophages, identified by Tim-4 expression, were found in the LP and S/M. Long-lived LP macrophages are restrained in their response to proinflammatory stimulation compared to short-lived populations in the same location, and to the long-lived population within the S/M. Employing a novel Timd4creTgfbr2fl/fl mouse line we demonstrate distinct functions of TGF-{beta} on long-lived macrophages in these two compartments. Importantly, in Timd4creTgfbr2fl/fl mice, zonation of CD163+ macrophages in the S/M was lost, suggesting TGF-{beta} plays an unappreciated role in positioning of macrophages in the tissue. These data highlight the importance of considering ontogeny and niche when assessing the action of key intestinal regulatory signals.

immunology↗

bioRxiv2023

Flowers are leakier than leaves but cheaper to build

- Producing and maintaining flowers is essential for reproduction in most angiosperms, underpinning population persistence and speciation. Although the physiological costs of flowers often oppose pollinator selection, these physiological costs have rarely been quantified. - We measured a suite of physiological traits quantifying the water and carbon costs and drought tolerance on flowers and leaves of over 100 phylogenetically diverse species, including water and dry mass contents, minimum epidermal conductance to water vapor (gmin), vein density, and dry mass per area. - Although there was substantial variation among species, flowers had significantly higher gmin and water content per unit area than leaves, but significantly lower vein density and dry mass per area than leaves. Both leaves and flowers exhibited similarly strong scaling between dry mass investment and water content. - The higher gmin of flowers offset their higher water content, suggesting that flowers may desiccate more rapidly than leaves during drought. The coordination between dry mass and water investment suggests that flowers rely on a hydrostatic skeleton to remain upright rather than on a carbon-based skeleton. For short-lived structures like flowers, water may be relatively cheaper than carbon, particularly given the relatively high amount of water loss per unit of carbon synthesized in photosynthesis.

plant biology↗

bioRxiv2021

Spatial proteogenomics reveals distinct and evolutionarily-conserved hepatic macrophage niches

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here, we present a spatial proteogenomic atlas of the healthy human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and bile-duct macrophages. We also uncover the respective spatially-resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that bile-duct macrophages are induced by local lipid exposure, while Kupffer cells crucially depend on their crosstalk with hepatic stellate cells via the evolutionarily-conserved ALK1-BMP9/10 axis.

immunology↗

bioRxiv2020

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

We dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cells in vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes.

immunology↗

bioRxiv2020

Single cell profiling of immature human postnatal thymocytes resolves the complexity of intra-thymic lineage differentiation and thymus seeding precursors.

During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow derived hematopoietic progenitors that migrate through the bloodstream. In human, the nature of these thymus immigrants has remained unclear. Here, we employ single-cell RNA sequencing on approximately 70.000 CD34+ thymocytes to unravel the heterogeneity of the human immature postnatal thymocytes. Integration of bone marrow and peripheral blood precursors datasets identifies several putative thymus seeding precursors that display heterogeneity for currently used surface markers as revealed by CITEseq. Besides T cell precursors, we discover branches of intrathymic developing dendritic cells with predominantly plasmacytoid DCs. Trough trajectory inference, we delineate the transcriptional dynamics underlying early human T-lineage development from which we predict transcription factor modules that drive stage-specific steps of human T cell development. Thus, our work resolves the heterogeneity of thymus seeding precursors in human and reveals the molecular mechanisms that drive their in vivo cell fate.

immunology↗