Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging

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....

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Published in:Endocrinology (Philadelphia) 2023-04, Vol.164 (4), p.1
Main Authors: Hong, Yourae, Kim, Hyun Jung, Park, Seongyeol, Yi, Shinae, Lim, Mi Ae, Lee, Seong Eun, Chang, Jae Won, Won, Ho-Ryun, Kim, Je-Ryong, Ko, Hyemi, Kim, Seon-Young, Kim, Seon-Kyu, Park, Jong-Lyul, Chu, In-Sun, Kim, Jin Man, Kim, Kun Ho, Lee, Jeong Ho, Ju, Young Seok, Shong, Minho, Koo, Bon Seok, Park, Woong-Yang, Kang, Yea Eun
Format: Article
Language:English
Subjects:
Aging
Aging (metallurgy)
Aging - genetics
Aging - metabolism
Analysis
B cells
Endocrinology
Epithelial cells
Epithelium
Fibrosis
Gene expression
Gene sequencing
Genes
Genetic aspects
Genetic transcription
Hormones
Humans
Hypothyroidism
Hypothyroidism - genetics
Inflammation
Maintenance
Major histocompatibility complex
Metabolism
Metallothionein
Ribonucleic acid
RNA
RNA sequencing
Single-Cell Analysis
Subpopulations
Thyrocytes
Thyroid
Thyroid gland
Thyroid Hormones
Thyroidectomy
Transcriptomics
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Summary: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.
ISSN:1945-7170
0013-7227
1945-7170
DOI:10.1210/endocr/bqad029