Biology subjects

Alves-Afonso, D.

Publications and source records attributed to Alves-Afonso, D..

3 recordsLinked to original sources

bioRxiv2025

Multi-omics Profiling of the Lateral Ventricle Choroid Plexus Reveals Developmental Cellular Remodeling, Early Immune Gene Activation, and a Novel Epithelial Subtype

Healthy brain development and function highly depend on the choroid plexus. Temporal alterations in the cellular landscape and gene expression of choroid plexus cells can alter immune cell trafficking in the brain and cerebrospinal fluid composition, ultimately impacting brain dynamics. Here, we performed a comprehensive multi-omics analysis--including bulk and single-cell transcriptomics and epigenomics--of the lateral ventricle choroid plexus across early postnatal and adult stages in mice and rats. We uncovered striking changes in the choroid plexus cellular composition from neonatal to adult stages, accompanied by transcriptional remodeling of all main cell types. Immune cells were markedly increased in adulthood and immune cell profiling revealed an altered cell-type diversity through time. Surprisingly, we observed an early gene activation of host-defense genes in all choroid plexus main cell types, beginning in the neonatal period and progressively increasing into young adulthood. Moreover, some genes induced in epithelial cells in response to inflammation were found to be epigenetically primed, despite not being transcriptionally active. Epithelial cells exhibited subtype diversity and plasticity, with distinct gene expression programs and chromatin accessibility profiles emerging over time. Notably, we identified a novel epithelial cell subtype with unique gene markers suggesting a specialized function potentially linked to neuro-signaling. Ligand-receptor interaction analysis revealed a progressive remodeling of cellular crosstalk networks during choroid plexus maturation, suggesting dynamic intercellular signaling as the tissue develops. Our study offers a comprehensive atlas of transcriptional activity and chromatin accessibility in choroid plexus cells, providing a valuable resource to guide future efforts in targeting gene expression at the choroid plexus for therapeutical purposes.

neuroscience↗

bioRxiv2023

Self-propagating wave drives noncanonical antidurotaxis of skull bones in vivo

Cell motility is a key feature of tissue morphogenesis, and it is thought to be driven primarily by the active migration of individual cells or collectives. However, this model is unlikely to apply to cells lacking overt cytoskeletal, stable cell-cell or cell-cell adhesions, and molecular polarity, such as mesenchymal cells. Here, by combining a novel imaging pipeline with biophysical modeling, we discover that during skull morphogenesis, a self-generated collagen gradient expands a population of osteoblasts towards a softer matrix. Biomechanical measurements revealed a gradient of stiffness and collagen along which cells move and divide. The moving cells generate an osteogenic front that travels faster than individual tracked cells, indicating that expansion is also driven by cell differentiation. Through biophysical modeling and perturbation experiments, we found that mechanical feedback between stiffness and cell fate drives bone expansion and controls bone size. Our work provides a mechanism for coordinated motion that does not rely upon the cytoskeletal dynamics of cell migration. We term this self-propagating motion down a stiffness gradient, noncanonical antidurotaxis. Identification of alternative mechanisms of cellular motion will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties.

biophysics↗

bioRxiv2021

Tissue scale properties of the extracellular matrix regulates nuclear shape, organisation and fate in the embryonic midline sutures

Balancing self-renewal and differentiation is a key feature of every stem cell niche and one that is tuned by mechanical interactions of cells with their neighbors and surrounding extracellular matrix. The fibrous stem cell niches that develop as sutures between skull bones must balance the complex extracellular environment that emerges to define them with self-renewal and bone production. Here, we address the role for physical stimuli in suture development by probing the relationship between nuclear shape, organization and gene expression in response to a developing collagen network in embryonic midline sutures. This work complements genetic approaches used to study sutures and provides the first quantitative analyses of physical structure in these sutures. By combining multiple imaging modalities with novel shape description, in addition to network analysis methods, we find the early emergence of a complex extracellular collagen network to have an important role in regulating morphogenesis and cell fate. We show that disrupted collagen crosslinking can alter ECM organization of midline sutures as well as stimulate expression of bone differentiation markers. Further, our findings suggest that in vivo, skeletal tissues can uncouple the response of the nuclear lamina from collagen mediated tissue stiffening seen in vitro. Our findings highlight a crucial relationship between the cellular microenvironment, tissue stiffness and geometry with gene expression in normal development and maintenance of progenitor fate in embryonic sutures.

developmental biology↗