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

被引:8
作者
Hong, Yourae [1 ,2 ,3 ]
Kim, Hyun Jung [4 ,5 ]
Park, Seongyeol [6 ]
Yi, Shinae [7 ]
Lim, Mi Ae [7 ]
Lee, Seong Eun [7 ]
Chang, Jae Won [8 ]
Won, Ho-Ryun [8 ]
Kim, Je-Ryong [7 ,9 ]
Ko, Hyemi [9 ]
Kim, Seon-Young [10 ]
Kim, Seon-Kyu [10 ]
Park, Jong-Lyul [10 ]
Chu, In-Sun [11 ]
Kim, Jin Man [12 ]
Kim, Kun Ho [13 ]
Lee, Jeong Ho [3 ,4 ]
Ju, Young Seok [4 ,6 ]
Shong, Minho [7 ,14 ]
Koo, Bon Seok [7 ,8 ]
Park, Woong-Yang [1 ,2 ]
Kang, Yea Eun [7 ,14 ]
机构
[1] Samsung Med Ctr, Samsung Genome Inst, Seoul, South Korea
[2] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea
[3] Katholieke Univ Leuven, Dept Oncol, Mol Digest Oncol, Leuven, Belgium
[4] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon, South Korea
[5] Korea Univ, Dept Anat, Coll Med, Seoul 02841, South Korea
[6] Genome Insight Technol, Daejeon, South Korea
[7] Chungnam Natl Univ, Res Inst Med Sci, Daejeon, South Korea
[8] Chungnam Natl Univ, Coll Med, Dept Otolaryngol Head & Neck Surg, Daejeon 35015, South Korea
[9] Chungnam Natl Univ, Coll Med, Dept Surg, Daejeon, South Korea
[10] Res Inst Biosci & Biotechnol, Personalized Genom Med Res Ctr, Daejeon, South Korea
[11] Korea Res Inst Biosci & Biotechnol, Genome Editing Res Ctr, Daejeon, South Korea
[12] Chungnam Natl Univ, Coll Med, Dept Pathol, Daejeon 35015, South Korea
[13] Chungnam Natl Univ Hosp, Dept Nucl Med, Daejeon, South Korea
[14] Chungnam Natl Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Daejeon, South Korea
基金
新加坡国家研究基金会;
关键词
thyroid; aging; single-cell RNA sequencing; metallothionein; fibrosis; MHC CLASS-I; OXIDATIVE STRESS; GENE-EXPRESSION; CYCLE ARREST; OLD MICE; METALLOTHIONEIN; OVEREXPRESSION; MOLECULES; DISEASE; REPRESSION;
D O I
10.1210/endocr/bqad029
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:12
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