The existence of multipotent adipose-derived stem cells isolated from human orbital fat (OF) tissue has shown great therapeutic potential in tissue engineering and regenerative medicine. But the use of stem cells for therapeutic applications is influenced by their proliferative and differentiation potentials, which may be affected by the age of the donor. So far there is little knowledge about the effects of donor age on the biological properties of human orbital adipose-derived stem cells (OASCs). The intraorbital fat protrusion in the lower eyelids occurs as an aging process, and the protruded fat is routinely removed during aesthetic surgeries. Based on the ease of OF harvest and the availability of OASCs, we investigated in this study the relationship between age and the differentiation and proliferation potentials of human OASCs. Human orbital adipose samples were harvested from young (with normal lower eyelid appearance) and old donors (having protruded fat pads in the lower eyelids). The morphological properties of orbital adipocytes were assessed and the fat cell size displayed a decreasing trend with advancing age. OASCs were isolated from the fat samples, expanded in vitro and cultured under appropriate inducive conditions. Compared to the young cells, although no difference was found in the cell yield and phenotype expression, aged OASCs showed fewer progenitor cell numbers, reduced proliferative rates, increased senescent features and decreased differentiation potentials towards adipogenic, osteogenic and chondrogenic lineages. Our data suggested that using autologous OASCs from elderly patients for potential therapeutic purposes might be restricted.
Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family, and FABP5 were significantly upregulated in cSCC cells. Further experiments confirmed their upregulation and showed that S100A9 or FABP5 knockdown in cSCC cells inhibited their proliferation and migration through NF-κB pathway. Taken together, our data provide a valuable resource for deciphering the molecular pattern in UV-induced cSCC at a single-cell level and suggest that S100A9 and FABP5 may provide novel targets for therapeutic intervention of cSCC in the future.
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