Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution
Xiaojing Yang1
Xichan Chen2
Wei Wang2
Siming Qu3
Binbin Lai4
Ji Zhang2
JIAN CHEN2
Chao Han2
Yi Tian2
Yingbin Xiao2
Weiwu Gao2*
Yuzhang Wu2*
- 1Chongqing University, China
- 2Army Medical University, China
- 3The First Affiliated Hospital of Kunming Medical University, China
- 4Peking University, China
Thymus is the main immune organ which is responsible for the production of self-tolerant and functional T cells, but it shrinks rapidly with age after birth. Although studies have researched thymus development and involution in mouse, the critical regulators that arise with age in human thymus remain unclear. We collected public human single-cell transcriptomic sequencing (scRNAseq) datasets containing 350,678 cells from 36 samples, integrated them as a cell atlas of human thymus. Clinical samples were collected and experiments were performed for validation. We found early thymocyte-specific signaling and regulons which played roles in thymocyte migration, proliferation, apoptosis and differentiation. Nevertheless, signaling patterns including number, strength and path completely changed during aging, Transcription factors (FOXC1, MXI1, KLF9, NFIL3) and their target gene, IGFBP5, were resolved and up-regulated in aging thymus and involved in promoting epithelial-mesenchymal transition (EMT), responding to steroid and adipogenesis process of thymic epithelial cell (TECs). Furthermore, we validated that IGFBP5 protein increased at TECs and Hassall's corpuscle in both human and mouse aging thymus and knockdown of IGFBP5 significantly increased the expression of proliferation-related genes in thymocytes. Collectively, we systematically explored cell-cell communications and regulons of early thymocytes as well as agerelated differences in human thymus by using both bioinformatic and experimental verification, indicating IGFBP5 as a functional marker of thymic involution and providing new insights into the mechanisms of thymus involution.
Keywords: IGFBP5, Thymus involution, single-cell RNA sequencing, thymic epithelial cell, thymocyte
Received: 16 Oct 2023;
Accepted: 03 Jan 2024.
Copyright: © 2024 Yang, Chen, Wang, Qu, Lai, Zhang, CHEN, Han, Tian, Xiao, Gao and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mx. Weiwu Gao, Army Medical University, Chongqing, 400038, China
Mx. Yuzhang Wu, Army Medical University, Chongqing, 400038, China