Biology subjects

Meziane, M.

Publications and source records attributed to Meziane, M..

4 recordsLinked to original sources

bioRxiv2026

Integrative vasculogenesis unifies distinct endothelial sources in the developing lung

How endothelial cells from distinct developmental sources are integrated into a single continuous vascular system remains unresolved. Here, using the developing mouse lung, we identify a mesenchymal progenitor population that generates endothelial cells de novo and incorporates them into the expanding vasculature through a mechanism we term integrative vasculogenesis. Genetic lineage tracing shows that these progenitors contribute directly to the pulmonary endothelium, defining a source distinct from endothelial cells of the major vessels. Live imaging and single-cell tracking reveal that newly specified angioblasts exhibit high motility, dispersing through stochastic migration before integrating into pre-existing vascular networks. Cell ablation demonstrates that pre-existing networks are required to support the migration, proliferation and survival of nascent endothelial cells. Integrative vasculogenesis is thus distinct from classical vasculogenesis and angiogenesis, providing a framework for how endothelial populations of different origins are assembled into a functional circulatory system.

developmental biology↗

bioRxiv2025

Reconstructing signaling histories of single cells via perturbation screens and transfer learning

Manipulating the signaling environment is an effective approach to alter cellular states for broad-ranging applications, from engineering tissues to treating diseases. Such manipulation requires knowing the signaling states and histories of the cells in situ, for which high-throughput discovery methods are lacking. Here, we present an integrated experimental-computational framework that learns signaling response signatures from a high-throughput in vitro perturbation atlas and infers combinatorial signaling activities in in vivo cell types with high accuracy and temporal resolution. Specifically, we generated signaling perturbation atlas across diverse cell types/states through multiplexed sequential combinatorial screens on human pluripotent stem cells. Using the atlas to train IRIS, a neural network-based model, and predicting on mouse embryo scRNAseq atlas, we discovered global features of combinatorial signaling code usage over time, identified biologically meaningful heterogeneity of signaling states within each cell type, and reconstructed signaling histories along diverse cell lineages. We further demonstrated that IRIS greatly accelerates the optimization of stem cell differentiation protocols by drastically reducing the combinatorial space that needs to be tested. This framework leads to the revelation that different cell types share robust signal response signatures, and provides a scalable solution for mapping complex signaling interactions in vivo to guide targeted interventions.

developmental biology↗

bioRxiv2024

Diffusion barriers imposed by tissue topology shape morphogen gradients

Animals use a small number of morphogens to pattern tissues, but it is unclear how evolution modulates morphogen signaling range to match tissues of varying sizes. Here, we used single molecule imaging in reconstituted morphogen gradients and in tissue explants to determine that Hedgehog diffused extra-cellularly as a monomer, and rapidly transitioned between membrane-confined and -unconfined states. Unexpectedly, the vertebrate-specific protein SCUBE1 expanded Hedgehog gradients by accelerating the transition rates between states without affecting the relative abundance of molecules in each state. This observation could not be explained under existing models of morphogen diffusion. Instead, we developed a topology-limited diffusion model in which cell-cell gaps create diffusion barriers, and morphogens can only overcome the barrier by passing through a membrane-unconfined state. Under this model, SCUBE1 promotes Hedgehog secretion and diffusion by allowing it to transiently overcome diffusion barriers. This multiscale understanding of morphogen gradient formation unified prior models and discovered novel knobs that nature can use to tune morphogen gradient sizes across tissues and organisms.

developmental biology↗

bioRxiv2020

Spindle alignment is uncoupled with Kar9 symmetry breaking

Spindle positioning must be tightly regulated to ensure asymmetric cell divisions are successful. In budding yeast, spindle positioning is mediated by the asymmetric localization of microtubule +end tracking protein Kar9. Kar9 asymmetry is believed to be essential for spindle alignment. However, the temporal correlation between symmetry breaking and spindle alignment has not been measured. Here, we establish a method of quantifying Kar9 symmetry breaking and find that Kar9 asymmetry is not well coupled with early spindle alignment. We report the majority of asymmetric cells are not stably aligned. Rather, stable alignment, a state we define as perfect alignment, is correlated with Kar9 localization to the bud compartment, regardless of symmetry state. Our findings suggest that Kar9 asymmetry alone is insufficient for perfect alignment and reveal a possible role for Swe1 in regulating spindle alignment efficiency.

cell biology↗