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

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.
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