Epidermal homeostasis: a balancing act of stem cells in the skin

Epidermal homeostasis: a balancing act of stem cells in the skin

2009 March ; 10(3): 207–217. doi:10.1038/nrm2636. | Cédric Blanpain * and Elaine Fuchs
The skin epidermis and its appendages, such as hair follicles and sebaceous glands, undergo continuous renewal through a process called homeostasis. Stem cells (SCs) play a crucial role in maintaining this process by providing new cells to replace those lost through normal turnover or injury. Different SC pools contribute to the maintenance and repair of various epidermal tissues. The mechanisms and signaling pathways that orchestrate epithelial morphogenesis in the skin are also involved in adult skin homeostasis. The skin barrier is essential for protecting animals from environmental stresses and facilitating thermal regulation, protection against radiation, and social interactions. Homeostasis in the skin is maintained by SCs in epithelial tissues, which replace keratinocytes lost through differentiation or cell death. Recent studies have begun to elucidate the mechanisms behind these processes. During embryonic development, the skin epidermis originates from the ectoderm and undergoes stratification, with the innermost layer producing a basement membrane rich in extracellular matrix proteins and growth factors. The epidermis adheres to this membrane, which serves as a growth-promoting platform and physical boundary. In adult life, the epidermis undergoes homeostatic regulation, with basal cells periodically executing their program of terminal differentiation and moving outwards. This process involves the expression of specific genes and the formation of robust cytoskeletal networks to resist mechanical stresses. Signaling pathways such as Notch, MAPK, NF-κB, and transcriptional regulators like p63, AP2, C/EBP, IRF6, GRHL3, and KLF4 are essential for proper epidermal stratification and barrier function. The basal to spinous switch, controlled by p63 and the canonical Notch pathway, is crucial for skin development and homeostasis. Asymmetric cell division is a key mechanism for maintaining SC equilibrium. Two types of asymmetric divisions have been described: one parallel to the basement membrane and another perpendicular to it. The second type, observed during embryonic development, provides a simple mechanism for asymmetrical partitioning of daughter cells with different fates. The hair follicle (HF) and interfollicular epidermis (IFE) are maintained by different resident SCs. HF SCs reside in a specialized microenvironment called the bulge, which is essential for hair cycling and development. Lineage-tracing experiments have shown that HF SCs generate and maintain the cycling portion of the HF during the growth phase of the hair cycle. Signaling pathways such as Wnt and BMP play significant roles in HF specification and activation during development and adult homeostasis. Wnt/β-catenin signaling is crucial for HF progenitor specification, while BMP signaling regulates SC quiescence and stimulates hair regeneration. The review highlights the similarities between embryonic development and adult homeostasis in the skin, emphasizing the importance of SCs in maintaining skin health and the complex regulatory mechanisms involved. Future research willThe skin epidermis and its appendages, such as hair follicles and sebaceous glands, undergo continuous renewal through a process called homeostasis. Stem cells (SCs) play a crucial role in maintaining this process by providing new cells to replace those lost through normal turnover or injury. Different SC pools contribute to the maintenance and repair of various epidermal tissues. The mechanisms and signaling pathways that orchestrate epithelial morphogenesis in the skin are also involved in adult skin homeostasis. The skin barrier is essential for protecting animals from environmental stresses and facilitating thermal regulation, protection against radiation, and social interactions. Homeostasis in the skin is maintained by SCs in epithelial tissues, which replace keratinocytes lost through differentiation or cell death. Recent studies have begun to elucidate the mechanisms behind these processes. During embryonic development, the skin epidermis originates from the ectoderm and undergoes stratification, with the innermost layer producing a basement membrane rich in extracellular matrix proteins and growth factors. The epidermis adheres to this membrane, which serves as a growth-promoting platform and physical boundary. In adult life, the epidermis undergoes homeostatic regulation, with basal cells periodically executing their program of terminal differentiation and moving outwards. This process involves the expression of specific genes and the formation of robust cytoskeletal networks to resist mechanical stresses. Signaling pathways such as Notch, MAPK, NF-κB, and transcriptional regulators like p63, AP2, C/EBP, IRF6, GRHL3, and KLF4 are essential for proper epidermal stratification and barrier function. The basal to spinous switch, controlled by p63 and the canonical Notch pathway, is crucial for skin development and homeostasis. Asymmetric cell division is a key mechanism for maintaining SC equilibrium. Two types of asymmetric divisions have been described: one parallel to the basement membrane and another perpendicular to it. The second type, observed during embryonic development, provides a simple mechanism for asymmetrical partitioning of daughter cells with different fates. The hair follicle (HF) and interfollicular epidermis (IFE) are maintained by different resident SCs. HF SCs reside in a specialized microenvironment called the bulge, which is essential for hair cycling and development. Lineage-tracing experiments have shown that HF SCs generate and maintain the cycling portion of the HF during the growth phase of the hair cycle. Signaling pathways such as Wnt and BMP play significant roles in HF specification and activation during development and adult homeostasis. Wnt/β-catenin signaling is crucial for HF progenitor specification, while BMP signaling regulates SC quiescence and stimulates hair regeneration. The review highlights the similarities between embryonic development and adult homeostasis in the skin, emphasizing the importance of SCs in maintaining skin health and the complex regulatory mechanisms involved. Future research will
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[slides and audio] Epidermal homeostasis%3A a balancing act of stem cells in the skin