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).<br><br>The cell lineage path of keratinocytes in interfollicular epidermis is depicted through four cell differentiation steps involving five distinct cellular states: keratinocyte stem cells of epidermal basal layer, transit amplifying cells, spinous keratinocytes, granular keratinocytes, and corneocytes. Each differentiation step is regulated by a distinct combination of regulatory molecules present in the microenvironment of differentiating cells.

毛囊间表皮位于附属器官（如毛囊、汗腺和皮脂腺）之间的皮肤表层。自真皮表皮交界处起，毛囊间表皮层包括基底层（stratum basale）、棘层（stratum spinosum）、颗粒层（stratum granulosum）和角质层（stratum corneum）。基底层由角蛋白细胞干细胞和过渡扩增细胞组成。棘层、颗粒层和角质层分别由棘层角蛋白细胞、颗粒层角蛋白细胞和角质细胞构成。毛囊间表皮具有高细胞周转率。角蛋白细胞干细胞在成年期间持续自我更新，并分化为过渡扩增细胞。过渡扩增细胞在分化前经历多个细胞周期，首先分化为棘层角蛋白细胞，然后为颗粒层角蛋白细胞，最终分化为角质细胞。角质细胞失去其细胞核和细胞质器官，形成扁平的鳞片，为抵御病原体入侵和水分流失提供物理屏障。欲详细了解，请参阅 Zijl 等人于 2022 年的综述，以及 Cheng 等人于 2018 年、Wang 等人于 2020 年、Aragona 等人于 2020 年、Haensel 等人于 2020 年、Negri 等人于 2023 年以及 Ganier 等人于 2024 年进行的单细胞转录组和空间转录组研究，这些研究为人类毛囊间表皮提供了更高分辨率的视角）。毛囊间表皮中的角蛋白细胞谱系路径通过四个细胞分化步骤和五个不同的细胞状态来描述：表皮基底层角蛋白细胞干细胞、过渡扩增细胞、棘层角蛋白细胞、颗粒层角蛋白细胞和角质细胞。每个分化步骤都受到不同分化细胞微环境中存在的特定调节分子的独特组合的调控。