TNFSF14⁺ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.

ABSTRACT: In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural kille

SUBMITTER: Shi JW 

PROVIDER: S-EPMC11535022 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature