A hierarchy of migratory keratinocytes maintains the tympanic membrane
Frumm, S. M.; Yu, K. S.; Chang, J.; Briscoe, J. A.; Lee, K. P.; Byrnes, L. E.; Sneddon, J. B.; Tward, A. D.
Show abstract
Although the conductive function of the tympanic membrane (TM) is critical for hearing, it is unknown how the organ maintains cellular homeostasis. Using a combination of single-cell RNA sequencing, lineage tracing, whole-organ explant, and live-cell imaging, we demonstrate that the stem cells of the TM epidermis reside in a distinct location at the superior portion of the TM and, as progeny migrate inferiorly, Pdgfra+ fibroblasts maintain a niche supporting proliferation of committed progenitors, while keratinocytes distal from the niche differentiate. Thus, the TM has a three dimensional differentiation hierarchy of keratinocytes distinct from that at other epidermal sites. The TM represents a physiological context where, in the absence of injury, keratinocytes both transit through a proliferative committed progenitor state and exhibit directional lateral migration. This work forms a foundation for understanding common disorders of the TM and introduces a new model system for the understanding of keratinocyte biology.
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