IGF-1R deficiency in human keratinocytes disrupts epidermal homeostasis and stem cell maintenance

Epidermal stem cells (ESCs) are keratinocytes that reside in the basal layer of the epidermis and mediate epidermal homeostasis. Insulin-like growth factor 1 (IGF-1) signaling through its receptor (IGF-1R) has been identified as an important regulator in rodent skin development and differentiation....

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Bibliographic Details
Published in:Journal of dermatological science 2019-05, Vol.94 (2), p.298-305
Main Authors: Muraguchi, Taichi, Nanba, Daisuke, Nishimura, Emi K., Tashiro, Tomoko
Format: Article
Language:English
Subjects:
Cell Differentiation
Cell Line
CRISPR-Cas9
Epidermis - physiology
Gene Knockout Techniques
Human skin equivalent
Humans
IGF-1/IGF-1R signaling
Insulin-Like Growth Factor I - metabolism
Keratinocyte
Keratinocytes - metabolism
Receptor, IGF Type 1 - genetics
Receptor, IGF Type 1 - metabolism
Signal Transduction
Stem Cells - physiology
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Summary:Epidermal stem cells (ESCs) are keratinocytes that reside in the basal layer of the epidermis and mediate epidermal homeostasis. Insulin-like growth factor 1 (IGF-1) signaling through its receptor (IGF-1R) has been identified as an important regulator in rodent skin development and differentiation. However, the role of IGF-1/IGF-1R signaling in human keratinocytes is not yet well understood. This study aimed to clarify the role of IGF-1/IGF-1R signaling in human epidermal homeostasis. IGF-1R specific knockout (KO) HaCaT keratinocytes were generated by CRISPR-Caspase-9-mediated non-homologous end joining frame-shift mutations. Further, the behavior of these keratinocytes in epidermal homeostasis was investigated using reconstructed epidermis and human skin equivalents. IGF-1R KO HaCaT keratinocytes were successfully established and produced thin epidermis in three-dimensional culture models. Keratin10-positive cells were frequently found in the basal layer of the reconstructed epidermis. IGF-1/IGF-1R signaling was demonstrated to play a key role in maintaining human epidermal homeostasis. This method provides a new framework to investigate gene function in human epidermal homeostasis.
ISSN:0923-1811
1873-569X
DOI:10.1016/j.jdermsci.2019.05.001