MRAP mediated adipocyte differentiation by thymic mesenchymal stromal cells contributes to thymic involution.

Dandan Wang, Xiang Fang, Yujun Deng, Xin Wen, Ousheng Liu, Junji Xu, Fudong Fan, Dongjin Wang, Yichen Han, Peter Zanvit, Sang A Park, Wenwen Jin, Hongbo Hu, Lingyun Sun, WanJun Chen

Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. · pubmed

Paper

Abstract

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution, but the underlying cellular and molecular mechanisms remain unknown. We show here that thymic mesenchymal stromal cells (tMSCs) have a higher tendency to differentiate into adipocytes and melanocortin-2 receptor accessory protein (MRAP) is a potential driver of tMSCs adipogenesis. Furthermore, we discover that thymosin-α1 promotes MRAP expression in tMSCs through FoxO1 signaling pathway. Additionally, the proportion of tMSCs increase in older mice compared to young mice. Importantly, MRAP is also necessary for human thymic MSCs to differentiate into adipocytes when exposed to thymosin-α1. Single-cell RNA-seq analysis of human thymus revealed an accumulation of tMSCs and adipocytes during aging, indicating a strong potential for adipogenic differentiation in age-related thymic involution. Thus, we have revealed MRAP as a key factor in promoting thymic MSCs adipogenesis triggered by thymosin-α1 and FoxO1 pathway, which may serve as potential target to hinder adiposity in age-related thymic involution.

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Research summary

MRAP is identified as a key factor promoting adipogenic differentiation in thymic mesenchymal stromal cells, which contributes to age-related thymic involution. The study addresses a potential mechanism underlying aging processes, specifically the differentiation of stem cells into adipocytes, which is relevant to understanding and potentially mitigating age-related changes in the thymus.

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