Cochlear Fibrocyte and Osteoblast Lineages Expressing Type 2 Deiodinase Identified with a Dio2CreERt2 Allele

Type 2 deiodinase (Dio2) amplifies levels of 3,5,3'-L-triiodothyronine (T3), the active form of thyroid hormone, and is essential for cochlear maturation and auditory development. However, cellular routes for endocrine signaling in the compartmentalized, anatomically complex cochlea are little understood. Dio2 generates T3 from thyroxine (T4), a more abundant thyroid hormone precursor in the circulation, and is dramatically induced in the cochlea before the onset of hearing. The evidence implies that specific Dio2-expressing cell types critically mediate T3 signaling but these cell types are poorly defined because Dio2 is expressed transiently at low levels. Here, using a Dio2(creERt2) knockin that activates a fluorescent reporter, we define Dio2-expressing cochlear cell types at high resolution in male or female mice. Dio2-positive cells were detected in vascularized supporting tissues but not in avascular internal epithelia, indicating segregation ofT3-generating andT3-responding tissues. In the spiral ligament and spiral limbus, Dio2-positive fibrocytes clustered around vascular networks that conveyT4 into cochlear tissues. In the otic capsule, Dio2-positive osteoblasts localized at cartilage surfaces as the bony labyrinth matures. We corroborated the identities of Dio2-positive lineages by RNA-sequencing of individual cells. The results suggest a previously unrecognized role for fibrocytes in mediating hormonal signaling. We discuss a model whereby fibrocytes mediate paracrine-like control of T3 signaling to the organ of Corti and epithelial target tissues.

Automated summary

Type 2 deiodinase (Dio2) is essential for auditory development by amplifying the active form of thyroid hormone, 3,5,3'-L-triiodothyronine (T3). A study using Dio2(creERt2) knockin mice identified Dio2-expressing cell types in the cochlea, with fibrocytes potentially playing a key role in mediating hormonal signaling. The findings suggest a novel mechanism where fibrocytes control T3 signaling to the organ of Corti and epithelial target tissues in a paracrine-like manner.