Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging
Yourae Hong, Hyun Jung Kim, Seongyeol Park, Shinae Yi, Mi Ae Lim, Seong Eun Lee, Jae Won Chang, Ho-Ryun Won, Je Ryong Kim, Hyemi Ko, Seon‐Young Kim, Seon‐Kyu Kim, Jong‐Lyul Park, In‐Sun Chu, Jin‐Man Kim, Kun Ho Kim, Jeong Ho Lee, Young Seok Ju, Minho Shong, Bon Seok Koo, Woong‐Yang Park, Yea Eun Kang
Abstract
The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into 5 distinct subpopulations, and a subset of cells was found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and major histocompatibility complex class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq datasets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.