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. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing of 54,726 cells derived from pathologically normal thyroid tissues from seven patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into five distinct subpopulations, and a subset of cells were found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and MHC class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq data sets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.

Identification of therapeutic targets for 18 clinical diseases by integrating human plasma proteome with genome

“…When compared to whole blood, CA12 was highly expressed in numerous tissues, including the thyroid ( p -value<0.001) ( Figure 2B ). To better understand the cell type of origin of CA12, we examined single-cell CA12 expression in human thyroid tissues from thyroidectomy patients (GSE182416, available at https://www.ncbi.nlm.nih.gov/geo/) [16]. CA12 was highly enriched in thyroid epithelial cells and fibroblasts in single-cell sequencing as compared to other cell types in adipose tissues ( p -value<0.001) ( Figure 2C ).…”

“…For data visualization, the dimension reduction approach UMAP (Uniform Manifold Approximation and Projection) was utilized. Cell type annotation was carried out in their study based on the specific gene expression [16].…”

“…Single-cell RNA-sequencing of 54,762 cells taken from normal thyroid tissue from 7 individuals who had thyroidectomy and had verified instances of differentiated thyroid carcinoma were retrieved from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/, GSE182416) [16]. Seurat 4.2.0 was used for processing and analyzing the single-cell dataset, as previously stated [13].…”

Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer

“…Age-related changes in insulin sensitivity and secretion can disrupt glucose homeostasis [ 86 , 87 ]. Thyroid function tends to decrease with age, leading to a decrease in metabolic rate and potential weight gain and changed metabolic pathways [ 88 , 89 ]. Moreover, dysregulation of cortisol secretion, often seen in chronic stress, can contribute to metabolic disturbances and accelerated aging [ 90 ].…”

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

“…To characterize putative causal cell types responsible for variation in thyroid function parameters within the reference range, single-cell RNA data of healthy thyroid tissue were used 42 . Of the investigated cell types (see Methods), genes identified in the TSH and low TSH GWASs were significantly enriched in thyroid epithelial cells (TSH p-value = 0.0004, low TSH p-value = 0.0009).…”