Biology subjects

Gueye, M.

Publications and source records attributed to Gueye, M..

5 recordsLinked to original sources

bioRxiv2024

A Light Sensitive Hyaluronic Acid-based Hydrogel for 3D Culturing, Differentiation, and Harvesting of Mesenchymal Stromal Cells

Hydrogels derived from natural sources are commonly used for 3D cell culturing due to their favourable interactions with cells. However, these biomaterials (e.g. Matrigel) suffer from variations in composition, limited mechanical tunability, the presence of xenogenic components and difficulties of cell retrieval. Semi-synthetic hydrogels are emerging to address these limitations, making these attractive for drug delivery and tissue engineering. Here, we describe a hydrogel platform based on hyaluronic acid (HA) modified by (1R,8S,9S)-bicycle[6.1.0]non-4-yn-9-ylmethanol (BCN) and a cross-linker composed of light sensitive o-nitrobenzyl moieties and polyethylene glycol (PEG) chains terminating in azides. The two components can undergo strain-promoted azide-alkyne cycloaddition (SPAAC) resulting in rapid gel formation. The stiffness of the hydrogel can be modulated by varying the crosslinker ratio and multi-functionalizing is possible by the incorporation of chemical cues modified by an azide. The fast hydrogelation enables easy encapsulation of cells and harvesting with preservation of viability is possible be short exposure to UV light. Moreover, it is demonstrated that visible light (405 nm) can soften the hydrogel resulting in phenotypical changes of human Mesenchymal Stromal Cells (hMSCs) co-cultured with endothelial colony-forming cells (ECFCs) with high viability. Our findings highlight that the photosensitive HA-based hydrogel provides a versatile and biocompatible platform for cell culture and tissue engineering applications, offering advantages over traditional 3D cell culturing platforms.

biochemistry↗

bioRxiv2023

Dissection and reconstruction of the colorectal cancer tumor microenvironment

Patient-derived organoids (PDOs) are the reference in vitro human disease models. However, the utility of colorectal cancer (CRC) PDOs is hindered by the lack of a tumor microenvironment (TME). To address this limitation, we built a living biobank of CRC PDOs with autologous stromal and immune TME. We characterized the original tumors and traditional monocultures using single-cell RNA-seq (scRNA-seq) and whole exome sequencing (WES) to obtain insights into cell type selection and phenotypic drift in culture. Subsequently, we developed culture conditions supporting all cell types to recapitulate the CRC-TME around PDOs. From the transcriptomes of >180k cells obtained from 260 such co-cultures, we illuminated the mutual influence of cells within CRC tumors. Based on original tumor data, atlases of predicted interactions and transcriptional networks elucidated why monocultures were altered and suggested that TME reconstruction more accurately reflected original tumor behavior. We found that inflammatory signals were absent in vitro and recovered upon co-culture with tumor-infiltrating lymphocytes (TILs). We also functionally confirmed that stromal, not cancer cells, mediated immune evasion. Additionally, stroma induced an invasive phenotype in cancer cells. From this deep dive into CRC-TME interactions, we built the human CRC-TME atlas (https://crc-tme.com/), an online portal for interactive exploration of gene expression data, prediction of cell-cell interactions at the pathway and receptor/ligand levels, transcriptional networks, and more. We anticipate PDO cultures with reconstructed TMEs will be valuable for discovery efforts, preclinical studies, and personalized medicine, with the atlas as a framework and inspiration for future CRC-TME studies.

cancer biology↗

bioRxiv2023

Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion Volumetric Printing of Microgels

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and therefore a bottleneck towards creating physiologically relevant models. Addressing this limitation, we introduced a novel technique, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing to spatially pattern multiple inks/cell types. Light-responsive microgels were developed as permissive microenvironment for cell homing and self-organization, and as bioresins ({micro}Resins) for light-based bioprinting. Tuning the mechanical and optical properties of these gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. {micro}Resins can then be sculpted within seconds with tomographic light projections into centimetre-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids within microgels enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP was applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with enhanced functionality, and for developing engineered living systems and (metabolic) disease models.

bioengineering↗

bioRxiv2020

Fonio millet genome unlocks African orphan crop diversity for agriculture in a changing climate

Sustainable food production in the context of climate change necessitates diversification of agriculture and a more efficient utilization of plant genetic resources. Fonio millet (Digitaria exilis) is an orphan African cereal crop with a great potential for dryland agriculture. Here, we established high-quality genomic resources to facilitate fonio improvement through molecular breeding. These include a chromosome-scale reference assembly and deep re-sequencing of 183 cultivated and wild Digitaria accessions, enabling insights into genetic diversity, population structure, and domestication. Fonio diversity is shaped by climatic, geographic, and ethnolinguistic factors. Two genes associated with seed size and shattering showed signatures of selection. Most known domestication genes from other cereal models however have not experienced strong selection in fonio, providing direct targets to rapidly improve this crop for agriculture in hot and dry environments.

plant biology↗

bioRxiv2018

A phylogenetic framework of the legume genus Aeschynomene for comparative genetic analysis of the Nod-dependent and Nod-independent symbioses

SUMMARYO_LISome Aeschynomene legume species have the property of being nodulated by photosynthetic Bradyrhizobium lacking the nodABC genes. Knowledge of this unique Nod (factor)-independent symbiosis has been gained from the model A. evenia but our understanding remains limited due to the lack of comparative genetics with related taxa using a Nod-dependent process.\nC_LIO_LITo fill this gap, this study significantly broadened previous taxon sampling, including in allied genera, to construct a comprehensive phylogeny. This backbone tree was matched with data on chromosome number, genome size, low-copy nuclear genes and strengthened by nodulation tests and a comparison of the diploid species.\nC_LIO_LIThe phylogeny delineated five main lineages that all contained diploid species while polyploid groups were clustered in a polytomy and were found to originate from a single paleo-allopolyploid event. In addition, new nodulation behaviours were revealed and Nod-dependent diploid species were shown to be tractable.\nC_LIO_LIThe extended knowledge of the genetics and biology of the different lineages in the legume genus Aeschynomene provides a solid research framework. Notably, it enabled the identification of A. americana and A. patula as the most suitable species to undertake a comparative genetic study of the Nod-independent and Nod-dependent symbioses.\nC_LI

plant biology↗