Project description:The retina is a light-sensitive highly-organized tissue, which is vulnerable to aging and age-related retinal diseases. However, the effects of aging on retinal cell types including those present in neural retina and retinal pigment epithelium (RPE), as well as cell types in choroid layer remain largely unknown. Here, we established the single-cell transcriptomic atlas of the retina and adjacent choroid in young and aged non-human primates (NHPs), identifying 15 cell types with distinct gene expression signatures and finding several novel markers. Our analysis reveals that oxidative stress is a major aging feature of the cells in the neural retinal layer, whereas an enhanced inflammatory response is that of RPE and choroidal cells. We also found that the RPE cell is the cell type most susceptible to aging in retina, as evidenced by the decreased cell density as well as the highest numbers of differentially expressed genes overlapping with genes underlying aging and aging-related retinal diseases, along with aberrant cell-cell interactions with its two adjacent layers. Altogether, our study provides the roadmap for understanding retinal aging in a NHP model at single-cell resolution, enabling the identification of new diagnostic biomarkers and potential therapeutic targets for age-related human retinal disorders.
Project description:Macrophages are the earliest emerging cells of the nascent immune system during embryonic development, and as innate immune cells constitutes an important first-line barrier against foreign organisms and pathogens. Rodent macrophages have been shown to infiltrate multiple organs at an early stage, developing symbiotically alongside these organs becoming tissue-resident macrophages (TRM) supporting tissue development and homeostasis. However, knowledge of the development and specialization of macrophages in the early human embryo is still limited. In order to study the spatiotemporal distribution and dynamic process of macrophage development in the early human embryo, we applied single-cell transcriptomic sequencing to generate a map of all CD45+CD235a- hematopoietic cells in human embryos of successive developmental stages from Carnegie stage (CS) 11 to 23. Here, we unravelled for the first time a map of macrophage heterogeneity across multiple anatomical sites and identified multiple macrophage subsets in the early human embryo, including various types of embryonic TRM (head, liver, lung and skin), and traced their developmental trajectories from yolk sac/embryonic liver-derived macrophages to their TRM specification in the head and liver based on core transcriptional factors. Altogether, our analyses provide a comprehensive characterization of the spatial and temporal dynamics of macrophage development in the early human embryo, and provides a reference for future study into human TRM function and embryonic development.
Project description:Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species and apoptosis were observed in granulosa cells from aged women. This study provides comprehensive understanding of the cell type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.