Biology subjects

Journot, R. P.

Publications and source records attributed to Journot, R. P..

3 recordsLinked to original sources

bioRxiv2025

Single-cell transcriptomics uncover conserved molecular mechanisms and functional diversification in multilayered epithelia

Multilayered epithelia, including skin, cervix, thymus, and prostate, arise from all three germ layers and perform diverse physiological functions, yet share a conserved layered architecture in which a supportive basal layer underlies differentiated suprabasal cells. To determine whether this common organization reflects a shared genetic program or tissue-specific regulation, we assembled a comprehensive single-cell atlas of 14 murine Multilayered epithelia. We identified a conserved p63-Notch axis that universally governs basal cell identity maintenance and suprabasal commitment. The p63-centered transcriptional program is shared, while Notch signaling recruits context-specific transcriptional modules to generate functional diversity. The layered architecture of epithelia spatially and temporally decouples conserved basal from context-specific suprabasal networks, compartmentalizing functional innovation across multilayered epithelia. Comparative genomics traces the p63-Notch axis to the root of vertebrates over 500 million years ago, showing that it was repeatedly co-opted through the incorporation of newly evolved genes in the suprabasal domain to generate novel epithelial functions. Our work establishes that evolution of multilayered epithelia operates through modular, compartmentalized diversification of a conserved scaffold, providing a unifying principle for how complex tissues achieve functional innovation while preserving structural integrity.

cell biology↗

bioRxiv2024

Conserved signals orchestrate self-organization and symmetry breaking of bi-layered epithelia during development and regeneration

Organ development relies on complex molecular mechanisms that guide initially homogeneous populations of stem cells to differentiate into specialized cell types within defined spatial patterns. While stable during homeostasis, the proper spatial organization of cell types must be re-established in case of tissue injury for successful regeneration of organ shape and function. How cells commit to a differentiation path is a central question in stem cell research; however, the coordination between tissue geometry and cell fate specification remains enigmatic. To elucidate the molecular mechanisms instructing self-organization and symmetry breaking of epithelial stem cells, we developed a multi-faceted approach combining in vitro organoids, ex vivo embryonic tissue explants, and single-cell quantitative imaging to investigate the dynamic acquisition of cell fate in four bi-layered epithelia, during embryonic development but also in regeneration. Our findings indicate that tissue architecture is the primary determinant of cell fate decisions in these tissues. Upon the initial cell internalization event, the homogeneous population of stem cell break symmetry. Through genetic and pharmacological perturbations, we have demonstrated that a tightly coordinated interplay between Hippo/YAP and Notch signaling is essential for conveying information from tissue architecture to functional cell differentiation and stem cell potency restriction. Globally, this study uncovers the inherent capacity of stem cells to self-organize into multicellular structures, where the precise position of each differentiated cell is critical to instruct their differentiation choices during embryonic development and regeneration.

developmental biology↗

bioRxiv2024

Contractile fibroblasts are recruited to the growing mammary epithelium to support branching morphogenesis

Fibroblasts are stromal cells found in connective tissue that are critical for organ development, homeostasis, and disease. Single-cell transcriptomic analyses have revealed a high level of inter- and intra-organ heterogeneity of fibroblasts. However, the functional implications and lineage relations of different fibroblast subtypes remain unexplored, especially in the mammary gland. Here we provide a comprehensive characterization of pubertal mammary fibroblasts, achieved using single-cell RNA sequencing, spatial mapping, and in vivo lineage tracing. Notably, we discovered a transient niche-forming population of specialized contractile fibroblasts that exclusively localize around the tips of the growing mammary epithelium and are recruited from the surrounding fat pad. Using functional organoid-fibroblast co-cultures we reveal that different fibroblast populations can acquire contractile features when in direct contact with the epithelium, promoting morphogenesis. In summary, our exhaustive characterization of these specialized cells provides new insights into mammary fibroblast heterogeneity and implicates their functional relevance for branching morphogenesis and lineage hierarchy during mouse mammary gland development.

developmental biology↗