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