A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane.

A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane. Cell Stem Cell. 2020 Nov 05;: Authors: Frumm SM, Yu SK, Chang J, Artichoker JA, Scaria SM, Lee KP, Byrnes LE, Sneddon JB, Tward AD Abstract The tympanic membrane (TM) is critical for hearing and requires continuous clearing of cellular debris, but little is known about homeostatic mechanisms in the TM epidermis. Using single-cell RNA sequencing, lineage tracing, whole-organ explant, and live-cell imaging, we show that homeostatic TM epidermis is distinct from other epidermal sites and has discrete proliferative zones with a three-dimensional hierarchy of multiple keratinocyte populations. TM stem cells reside in a discrete location of the superior TM and generate long-lived clones and committed progenitors (CPs). CP clones exhibit lateral migration, and their proliferative capacity is supported by Pdgfra+ fibroblasts, generating migratory but non-proliferative progeny. Single-cell sequencing of the human TM revealed similar cell types and transcriptional programming. Thus, during homeostasis, TM keratinocytes transit through a proliferative CP state and exhibit directional lateral migration. This work forms a foundation for understanding TM disorders and modeling keratinocyte biology. PMID: 33181078 [PubMed - as supplied by publisher]
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research