UNASSIGNED: The Notch signaling pathway orchestrates cell fate by either inducing cell differentiation or maintaining cells in an undifferentiated state. This study aims to evaluate Notch expression and function in normal @entity1 keratinocytes. @entity125 is expressed in all epidermal layers, though to a different degree of intensity, with a dramatic decrease during ageing. @entity125 intracellular domain (N1ICD) levels are decreased during transit from keratinocyte stem cells (KSC) to transit amplifying (TA) cells, mimicking survivin expression in samples from donors of all ages. @entity460 markedly reduces N1ICD levels in keratinocytes. N1ICD overexpression induces the up-regulation of survivin and the down-regulation of @entity7434 and involucrin, while increasing the S phase of the cell cycle. On the other hand, @entity125 inhibition (DAPT) dose-dependently decreases survivin, stimulates differentiation, and reduces keratinocyte proliferation in samples from donors of all ages. Silencing Notch downgrades survivin and increases @entity7434 . In addition, @entity125 inhibition decreases survivin levels and proliferation both in KSC and TA cells. Finally, while survivin overexpression decreases keratinocyte differentiation and increases N1ICD expression both in KSC and TA cells, silencing survivin results in N1ICD down-regulation and an increase in differentiation markers. These results suggest that the @entity125 /survivin crosstalk contributes to the maintenance of stemness in @entity1 keratinocytes.

Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in XXXX Keratinocytes during Ageing.

@entity1 :: ('9606', 'Species') :: ['human'] @entity125 :: ('4851', 'Gene') :: ['Notch1'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['Calcium'] @entity7434 :: ('3858', 'Gene') :: ['keratin 10']
@entity1 :: (9606,Species) :: ['Human']
