Notch Signaling in the Thyroid is Essential for Adult Homeostasis (scRNAseq thyroid)

Notch signaling between neighboring cells vitally contributes to specifying their identity and function, during development and in the adult. Here, we demonstrate that selective blockade of the Notch ligands JAG1 and JAG2 disrupts thermoregulation in adults by decreasing circulating thyroid hormones and thyroid function. By exploiting single-cell methods to carefully evaluate the thyroid, an understudied apex endocrine organ, we discovered unexpected thyrocyte heterogeneity, marked by three distinct thyrocyte subtypes with different Notch activation patterns. Overall design: Male mice of 10-12 weeks were treated with a single intraperitoneal injection of the Notch blocking antibodies (aJ1aJ2: 20mg/kg each; aN1aN2: 5, 10 mg/kg respectively; and anti-Ragweed isotype control: 40 mg/kg). 6 thyroids per sample were extracted at the time of necropsy, cut with a razor blade and digested in pool with 0.05mg/ml Liberase TM for 30min at 42C to isolate single cells.