MXD4/MAD4 Regulates Human Keratinocyte Precursor Fate.
J Invest Dermatol
; 143(1): 105-114.e12, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36007550
Deciphering the pathways that regulate human epidermal precursor cell fate is necessary for future developments in skin repair and graft bioengineering. Among them, characterization of pathways regulating the keratinocyte (KC) precursor immaturity versus differentiation balance is required for improving the efficiency of KC precursor ex vivo expansion. In this study, we show that the transcription factor MXD4/MAD4 is expressed at a higher level in quiescent KC stem/progenitor cells located in the basal layer of human epidermis than in cycling progenitors. In holoclone KCs, stable short hairpin-RNAâmediated decreased expression of MXD4/MAD4 increases MYC expression, whose modulation increases the proliferation of KC precursors and maintenance of their clonogenic potential and preserves the functionality of these precursors in three-dimensional epidermis organoid generation. Altogether, these results characterize MXD4/MAD4 as a major piece of the stemness puzzle in the human epidermis KC lineage and pinpoint an original avenue for ex vivo expansion of human KC precursors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
/
Células Epidérmicas
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article