Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin

The interfollicular epidermis is the skin surface layer in between the adnexa (hair follicles, sweat glands, and sebaceous glands). Going from the dermal epidermal junction, the interfollicular epidermis strata include the basal layer (stratum basale), spinous layer (stratum spinosum), granular layer (stratum granulosum), and the cornified layer (stratum corneum). The basal layer consists of keratinocyte stem cells and transit amplifying cells. The spinous, granular, and cornified layers consist of spinous keratinocytes, granular keratinocytes, and corneocytes, respectively. Interfollicular epidermis has a high cell turnover rate. Keratinocyte stem cells self renew throughout adulthood and give rise to transit amplifying cells. Transit amplifying cells undergo several cell cycles before committing to differentiation, first into spinous layer keratinocytes, then into granular layer keratinocytes, and finally into corneocytes. Corneocytes lose their nuclei and cytoplasmic organelles, forming flattened squames that provide a physical barrier against the invasion of pathogens and loss of bodily fluids. For a detailed review, please refer to Zijl et al. 2022, and for the single cell transcriptomic and spatial transcriptomic studies that provide a higher resolution view of human interfollicular epidermis, please refer to Cheng et al. 2018, Wang et al. 2020, Aragona et al. 2020, Haensel et al. 2020, Negri et al. 2023, and Ganier et al. 2024).

Summary from Reactome (R-HSA-9725554), read 2026-09-23.