75 / 2026-04-05 19:22:18

JMJD6 Regulates Chromatin Architecture via Alternative Splicing in Retinoic Acid Induced Differentiation of FGSCs

Female germline stem cell | Alternative splicing | Retinoic acid | JMJD6 | Hi-C

Female germline stem cells (FGSCs) are a group of adult stem cells that possess dual characteristics of self-renewal and capacity to proliferate. Retinoic acid (RA) is an active metabolic derivative that has been reported to induce the differentiation of FGSCs. Alternative splicing (AS) plays a critical role in germline cells development. However, its involvement in FGSCs differentiation has not been previously characterized. Here, we induced FGSC differentiation using RA and performed a comprehensive analysis of alternative splicing events. We found that Jumonji domain–containing protein 6 (JMJD6) regulates RA-induced FGSCs differentiation through alternative splicing. Mechanistically, JMJD6 undergoes alternative splicing during RA-induced FGSCs differentiation, generating isoforms that reshape higher-order chromatin architecture. This remodeling regulates chromatin loop strength at key differentiation and meiosis genes, thereby controlling their expression and driving FGSCs differentiation. Our study provides the first evidence that JMJD6 influences FGSCs differentiation through alternative splicing and offers new mechanistic insights relevant to reproductive disorders, including infertility and premature ovarian insufficiency.