Biology subjects

Sanchis-Calleja, F.

Publications and source records attributed to Sanchis-Calleja, F..

3 recordsLinked to original sources

bioRxiv2026

Luminal epithelium remodeling underlies endometrial regeneration during menstruation and pregnancy

Menstruation and pregnancy impose an immense regenerative burden on the endometrium. These events breach the luminal epithelium lining the uterine cavity, which is proposed to be replenished by cells in adjoining epithelial glands. In contrast to this gland-centric model, we find that luminal and glandular epithelia are maintained by separate progenitor populations during homeostasis, induced menstruation, pregnancy, and postpartum repair in mice. Although our data indicate that gland cells do not contribute substantially to luminal epithelium regeneration under physiological conditions, we find that they can serve as facultative progenitors that resurface the tissue after chemical ablation. During menstruation, the luminal epithelium bypasses the need for gland contributions by undergoing extensive expansion and morphogenesis to re-epithelialize stromal surfaces concurrently with tissue breakdown. Analogous morphogenesis occurs during gestation, revealing luminal epithelial expansion as a unifying mechanism enabling simultaneous stromal disruption and re-epithelialization, which may underlie the endometrium's remarkable regenerative capacity.

developmental biology↗

bioRxiv2025

CellFlow enables generative single-cell phenotype modeling with flow matching

High-content phenotypic screens provide a powerful strategy for studying biological systems, but the scale of possible perturbations and cell states makes exhaustive experiments unfeasible. Computational models that are trained on existing data and extrapolate to correctly predict outcomes in unseen contexts have the potential to accelerate biological discovery. Here, we present CellFlow, a flexible framework based on flow matching that can model single cell phenotypes induced by complex perturbations. We apply CellFlow to various phenotypic screens, accurately predicting expression responses to a wide range of perturbations, including cytokine stimulation, drug treatments and gene knockouts. CellFlow successfully modeled developmental perturbations at the whole-embryo scale and guided cell fate and organoid engineering by predicting heterogeneous cell populations arising from combinatorial morphogen treatments and by performing a virtual organoid protocol screen. Taken together, CellFlow has the potential to accelerate discovery from phenotypic screens by learning from existing data and generating phenotypes induced by unseen conditions.

bioinformatics↗

bioRxiv2024

Decoding morphogen patterning of human neural organoids with a multiplexed single-cell transcriptomic screen

Morphogens, secreted signalling molecules that direct cell fate and tissue development, are used to direct neuroepithelial progenitors towards discrete regional identities across the central nervous system. Neural tissues derived from pluripotent stem cells in vitro (neural organoids) provide new models for studying neural regionalization, however, we lack a comprehensive survey of how the developing human neuroepithelium responds to morphogen cues. Here, we produce a detailed map of morphogen-induced effects on the axial and regional specification of human neural organoids using a multiplexed single-cell transcriptomics screen. We find that the timing, concentration, and combination of morphogens strongly influence organoid cell type and regional composition, and that cell line and neural induction method strongly impact the response to a given morphogen condition. We apply concentration gradients in microfluidic chips or a range of static concentrations in multi-well plates to explore how human neuroepithelium interprets morphogen concentrations and observe similar dose-dependent induction of patterned domains in both scenarios. Altogether, we provide a detailed resource that supports the development of new regionalized neural organoid protocols and enhances our understanding of human central nervous system patterning.

developmental biology↗