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

## TL;DR

The study identifies MRAP as a key driver of fat cell formation in the thymus during aging, offering a new mechanism for thymic involution.

## Contribution

The novel contribution is identifying MRAP as a critical factor in thymic mesenchymal stromal cell adipogenesis during thymic involution.

## Key findings

- tMSCs show increased adipogenic potential with age and MRAP drives this process.
- Thymosin-α1 promotes MRAP expression via the FoxO1 signaling pathway in tMSCs.
- Single-cell RNA-seq reveals tMSC and adipocyte accumulation in aging human thymus.

## 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.

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Here, the authors show that MRAP is a key factor in promoting thymic MSCs adipogenesis triggered by thymosin-α1 and FoxO1 pathway, which provide a new mechanism for age-related thymic involution