Project description:Alkali burns cause rapid corneal remodeling, which is characterized by fibrosis, neovascularization, and immune infiltration; however, the cellular dynamics driving these responses remain poorly understood. Here, we present the first single-cell transcriptomic atlas of the rabbit cornea on day 14 postalkali injury, capturing the cellular and molecular architecture of stromal fibrosis. Single-cell RNA sequencing of naïve and injured corneas identified 14 transcriptionally distinct populations, including keratocytes, EMT-like epithelial cells, immune infiltrates, and heterogeneous fibroblast subtypes. Injury induced the expansion of ECM-remodeling fibroblasts and immune cells, accompanied by widespread transcriptional reprogramming. Stromal subclustering revealed four fibroblast states—quiescent, activated, proliferative, and progenitor-like—each with distinct gene signatures and functions. Pseudotime analysis revealed a trajectory from proliferative fibroblasts to ECM-secreting myofibroblasts, marked by stage-specific activation of mitotic, matrix, and contractile programs. Ligand–receptor inference via CellChat identified coordinated signaling through the TGFβ, PDGF, VEGF, and FGF pathways, alongside lesser-known axes such as NAMPT and NECTIN, implicating stromal–vascular crosstalk and metabolic stress in fibrotic progression. This study provides a comprehensive cellular framework for alkali-induced corneal fibrosis and identifies actionable targets for antifibrotic and antiangiogenic intervention in ocular surface disease.
Project description:Analysis of myocardial cellular gene expression during pressure overload reveals matrix based functional intercellular communication
Project description:Mechanotherapy promotes extracellular matrix remodeling in aged rat muscle recovering from disuse by reprogramming intercellular communication
Project description:In the social amoebae (Dictyostelia) quorum sensing system mediates aggregation of single cells into multicellular aggregates by chemotactic movement towards gradients of diffusible molecules known as acrasins. The acrasin of P. violaceum is the unusual dipeptide N-propionyl-gamma-L-glutamyl-L-ornithine-delta-lactam-ethylester, known as glorin. Phylogenetic analysis has indicated that P. violaceum is more related to the most derived group 4 dictyostelids than to the ancient group 2 polysphondylids such as P. pallidum. Nevertheless it has been reported that P. pallidum cells respond to glorin in chemotaxis assays. This has led to the assumption that glorin-based communication may be the most ancient form of intercellular communication that Dictyostelia invented to organize early steps of multicellular development. In this study we show that glorin mediates rapid changes in gene expression at the transition from vegetative growth to aggregation, apparently without pronounced cross-talk with the cyclic AMP-based communication system that coordinates post-aggregation events in this species. We describe glorin-mediated changes in gene expression in the social amoeba Polysphondylium pallidum at the transition from unicellular growth to multicellular development. Comparison of gene expression in growing cells versus cells starving for 2 or 3 hours in the presence or absence of glorin.
Project description:The human genome encodes ~1,900 secreted proteins, many of which mediate intercellular communication. Secreted proteins do not act cell-autonomously, limiting systematic approaches to characterize their functions. Here we introduce SecAct (Secreted Activity, https://secact.ccr.cancer.gov ), a computational framework that infers the signaling activities of 1,170 human secreted proteins from spatial, single-cell and bulk transcriptomic data. The inference model harnesses precomputed intercellular signaling signatures trained on 1,258 spatial transcriptomics samples spanning 37 cancer types. Transcriptomics data from antisecreted protein therapies validate SecAct's accuracy in predicting the repression of secreted protein activity following treatment. For spatial and single-cell transcriptomics data, SecAct provides interactive modules for analyzing secreted protein-mediated cell-cell communication. Applying SecAct to 54 cancer immunotherapy cohorts comprising 5,174 patients, we identified secreted proteins associated with tumor immunity. In vivo experiments validated lymphocyte antigen 86 (LY86), whose function in cancer was previously unknown, as an antitumor regulator.