Project description:Lens epithelial cells (LECs) are crucial for lens transparency and function. Aging disrupts LEC homeostasis and contributes to the development of age-related cataracts (ARCs). The lens epithelium may rely on adult stem/progenitor cells to sustain homeostasis and counteract aging-related factors. While the existence of stem cells in the lens epithelium has been supported by various studies, identifying these cells remains challenging. Recent advancements in single-cell RNA sequencing (scRNA-seq) provide high-resolution insights into cellular heterogeneity and offer a promising approach to elucidate the presence, origin, and age-related changes of lens stem/progenitor cells. We collected human donor lenses with ethical approval for scRNA-seq analysis, including samples from four non-aged (<65 years) and four aged (>65 years) individuals. After quality assessment and filtering, the transcriptome profiles of a total of 56,717 cells from two groups were depicted and merged to allow identification of overlapping cell populations in the following analysis. Subsequent analyses involved cell (sub)type characterization, trajectory inference, and cell-cell communication. Six types of lens superficial cells were identified by scRNA-seq, including four categories of LECs: early differentiation state LECs (eLECs), middle differentiation state LECs (mLECs), late differentiation state LECs (lLECs), and transient amplifying cells (TACs), along with a small number of lens fibre cells and immune cells.
Project description:Aging is a global problem, in which lung aging is accompanied by functional decline and structural disorders, disturbing the health of the elderly population. To explore anti-aging methods, we constructed a dynamic atlas of 45 cell types, from embryonic development to aging on human lung samples, and we hoped to use the discoveries of development to solve the problems of aging. During development and aging, epithelial and immune cells underwent a process of acquisition and loss of obligatory function. During aging, we identified cellular phenotypic changes that result in decreased pulmonary compliance and immune homeostasis. Furthermore, we found a characteristic expression pattern for the ferritin light chain (FTL) gene, which was regulated upward during development and downward during aging in multiple component cells of the lung.
Project description:Aging is a multifactorial process with significant functional alterations of the human body including endocrinal systems which control the whole-body physiology and metabolism. In this vein, aging-induced decline of endocrine function are associated with multiple physiological and metabolic diseases. However, aging-associated molecular shifts in the pituitary gland, the central organ of the endocrine system, have not been dissected systemically. In this study, we conducted single-cell transcriptomic analysis of the anterior pituitary gland by comparing old and young male mice. Single-cell transcriptomics not only increased the resolution for clustering of various cell types in the pituitary gland, but also enabled detailed analysis of differential expression and intercellular communication caused by aging. In summary, our study constructed the first single-cell transcriptomic atlas of pituitary aging and identified associated features of in a single-cell level, providing resources to develop novel potential therapeutic targets for aging-associated endocrine dysfunction.
Project description:Purpose: Molecular mechanisms of penile corpus cavernosum aging and male age-related erectile dysfunction (ED) remain unclear. Here we profiled young and old rat penile corpus cavernousm by single-cell RNA sequencing (scRNA-seq). Methods:To map the single-cell transcriptomic landscape of penile corpus cavernosum during aging, we performed uniform manifold approximation and projection (UMAP), differential gene expression analysis (DGEs), pseudotime analysis and single-cell entropy algorithm to dissect cellular composition and transcriptional heterogeneity. For validation analysis, we further performed immunofluorescence studies on key molecules involved during penile corpus cavernosum aging. Results: After stringent filtering,transcriptomes of 14,879 single cells (8,557 young and 6,322 old) derived from penile corpus cavernosum of 5 young (3 months) and 5 old (23 months) rats were analyzed subsequently. Clustering analysis of cell-type specific gene expression identified 19 cell types, such as smooth muscle cells, endothelial cells, fibroblasts,myofibroblasts and immune cells.Transcriptomic analyses revealed that transcriptional alterations across all cell types exhibited distinct properties rather than universally consistent. DGEs analysis demonstrated that genes related to extracellular matrix organization were highly expressed. Among these cell types, fibroblasts showed apparent heterogeneities. By performing pseudotime and single-cell entropy analysis on fibroblasts, we observed the age-associated decrease of entropy, and aged fibroblasts were found to adopt senescent secretory phenotype, as evidenced by the high expression of genes associated with the senescence-associated secretory phenotype (SASP). Since eliminating senescent cells or SASP were demonstrated to improve health and life span, we further investigated the distinct senescence-related gene expression signatures across all cell types during aging. Conclusions: We plotted a cellular atlas of penile corpus cavernosum, and revealed the molecular alterations of aging cells, especially fibroblasts. Our work will deepen the understanding of the heterogeneity among certain cell types during penile corpus cavernosum aging and provide novel entry points for the age-associated ED treatment.