Age-associated Transcriptional Patterns of Human Scalp Cells by Single Cell RNA Sequencing and Spatial Transcriptomics

Skin is a highly heterogeneous and dynamic organ which differs a lot in function and density of appendages - hair follicles, sebaceous glands, and sweat glands - in different body sites. Skin aging, which has the earlier visible signs such as hair loss and graying, is important to understand the molecular mechanisms of aging in a cell-type-specific manner. Combined with single-cell RNA sequencing and spatial transcriptomic technologies, we studied the age-related transcriptional patterns associated with age in 57,181 cells from 11 scalp samples. Three subtypes of mitotic keratinocytes, which were in the intermediate stage in the trajectory analysis, were identified to localize in the IFE, ORS, and hair matrix by deconvolution in the spatial chip. Feature genes in the dermal sheath were different across humans and mice. Stress-related transcription factors (such as JUND, JUN, FOS, FOSB, JUNB) were activated in the middle-age group. The DCT gene was upregulated in melanocytes in the middle-age group. BMP and non-canonical WNT signaling were decreased in the intercellular communication between dermal papillae and other cells in the middle-aged group. These findings provide cell-type-specific transcriptional clues to the aging process of skin as well as its appendages.