PT  - JOURNAL ARTICLE
AU  - Stacey M. Frumm
AU  - Kevin Shengyang Yu
AU  - Joseph Chang
AU  - Jordan A. Briscoe
AU  - Katharine P. Lee
AU  - Lauren E. Byrnes
AU  - Julie B. Sneddon
AU  - Aaron D. Tward
TI  - A hierarchy of migratory keratinocytes maintains the tympanic membrane
AID  - 10.1101/687947
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 687947
4099  - http://biorxiv.org/content/early/2019/07/01/687947.short
4100  - http://biorxiv.org/content/early/2019/07/01/687947.full
AB  - 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.