Interfollicular Epidermal Differentiation is Gradualistic Rather than Stepwis with GRHL3 Controlling Progression from Stem to Transition Cell States
- Author(s): Lin, Ziguang
- Advisor(s): Andersen, Bogi
- et al.
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.