Single-cell sequencing reveals the intermediate cell state and function of dermal papilla cells in the hair follicle cycle of cashmere goats

Abstract Background: Human hair loss and regeneration has stimulated interest in the natural hair cycle worldwide; however, such research is difficult because the periodicity of human or mouse hair is not visually obvious. Dermal papilla cells (DP cells) play an important role in the development of hair follicles, but knowledge of the differentiation and mechanisms of DP stem cells during transition through the hair follicle cycle are still limited, although some studies have reported that DP cells may have an intermediate cell state during differentiation, the classification and function of specific cell states are not clear. Results: Here, we used cashmere goats, that have obvious periodicity of hair follicles, as model animals and, based on unbiased single cell RNA sequencing, we identified and isolated DP cell data. Pseudotime ordering analysis was used to successfully construct a DP cell lineage differentiation trajectory and revealed the sequential activation of key genes, signaling pathways, and functions involved in cell fate decisions. At the same time, we analyzed the mechanisms of different cell fates and revealed the function of four different intermediate cells: Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are suggested to be DP progenitor cells. Conclusions: In development and apoptosis, inner bulge cells not only earlier than outer bulge cells, but occurred faster and was more thorough,this helps a deeper understanding of the role of bulge cells. Pseudogenes play another important role in function which promoted the competitive endogenous RNA (ceRNA) hybridization of pseudogenes.In different hair follicle cycles, DP cells will differentiate into different intermediate state cells and perform different functions, and the marker genes of the cells also changed. Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are DP progenitor cells, this conclusion provides an unprecedented deeper understanding of the function of DP cells.