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:Human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo,we tried to activate proliferation of HCEC by inhibiting cyclin-dependent kinase inhibitors.We have here demonstrated microarray data of transduced human corneal endothelial cell lines. Affymetrix human U133 plus 2.0 array was used to transcriptionally profile to compare cultured human corneal endothelial cells and transduced human corneal endothelial cells.
Project description:The transparency of lens relies on proper intercellular communication. Exosomes are crucial mediators of intercellular communication and play a key role in organ homeostasis and development. However, their presence and dynamics in the lens remain unclear. This study aimed to investigate the existence of endogenous exosomes in the lens and explore their potential functions. Using the cryaa promoter to drive Cd63-AcGFP expression, we achieved lens-specific exosome labeling in zebrafish. Live imaging revealed the presence of exosomes in lens cells during development and their movement trajectory under physiological conditions. Additionally, lens-derived exosomes (lens-Exos) facilitate communication not only between lens cells but also with surrounding tissues. We also identified that the biogenesis of Cd63+ exosomes in the lens is regulated by the Syntenin-a pathway. As knockdown of Syntenin-a in zebrafish resulted in delayed lens development, indicating a potential role for exosomes in normal lens development. Furthermore, in vitro hESC-lentoid induction showed that extracellular vesicles from ROR1+ lens progenitor cells (ROR1+ LPCs-EVs) promote lentoid differentiation. Proteomic analysis provided insights into the functions of ROR1+ LPCs-EVs. Overall, our study is the first to observe endogenous exosomes in the lens, providing new insights into lens pathophysiology and a potential strategy for modulating the lens microenvironment.