Ferroptosis Profiles of Human Mesenchymal Stromal Cell Subsets at the Single-Cell Level

Mesenchymal stromal cells (MSCs) have been widely used in clinical trials for various diseases, due to their broad differentiation potential and effective immunomodulatory effects. However, the cell death profiles of MSC subsets remain inadequately characterized. In this study, we unexpectedly identified unique differentially expressed ferroptotic genes in MSC subsets from four different tissues (adipose, bone marrow, dermis, and umbilical cord) and revealed a critical role of ferroptosis in umbilical cord derived MSCs (UC-MSCs). Furthermore, increased ferroptosis level and ferroptosis sensitivity were detected in the C1 subset of UC-MSCs, and the upregulation in the ferroptosis level and sensitivity was examined during an expansion of UC-MSCs with the treatment with an ferroptosis inducer. In addition, we detected an increase in the proportion of C1 UC-MSCs after treatment with a ferroptosis inducer (Erastin) or inhibitor (Fer-1). Overall, this study further revealed the intricate nature of MSCs and will help facilitate the use of optimal subtypes to improve their clinical efficacy in the future.