First Author | Frumm SM | Year | 2021 |
Journal | Cell Stem Cell | Volume | 28 |
Issue | 2 | Pages | 315-330.e5 |
PubMed ID | 33181078 | Mgi Jnum | J:335053 |
Mgi Id | MGI:6710393 | Doi | 10.1016/j.stem.2020.10.006 |
Citation | Frumm SM, et al. (2021) A Hierarchy of Proliferative and Migratory Keratinocytes Maintains the Tympanic Membrane. Cell Stem Cell 28(2):315-330.e5 |
abstractText | 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. |