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Interfollicular Epidermal Differentiation is Gradualistic Rather than Stepwis with GRHL3 Controlling Progression from Stem to Transition Cell States

Creative Commons 'BY' version 4.0 license

Although interfollicular epidermal (IFE) differentiation is thought to be

stepwise as reflected in sharp boundaries between the basal, spinous, granular

and cornified layers, this prediction has not been studied at a single cell

resolution. We used single cell RNA-seq to show that IFE differentiation is best

described as a single step gradualistic process with a large number of transition

cells between the basal and spinous layer. RNA-velocity analysis identifies a

commitment point that separates the plastic basal and transition cell state from

the unidirectionally differentiating cells. We also show that GRHL3, best known

for promoting IFE terminal differentiation, has a major function in suppressing

epidermal stem cell expansion and the emergence of an abnormal stem cell state

by suppressing Wnt signaling in stem cells.

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