Title: Lysosomal Catalytic Activity Promotes the Exit of Murine Totipotent 2-Cell State by Silencing Early-Embryonic Retrotransposons
Time: December 17, 2024, from 10:00 AM to 11:30 AM
Location: Wisdom Classroom 404, Zhi Zhen Building, Ningbo University Health Science Center
Speaker: Fu Xudong
Abstract:
During the early embryonic development of mice, totipotent two-cell (2C) embryos transiently express a series of retrotransposons/genes. These two-cell transcripts are rapidly silenced as the embryo exits the two-cell stage, facilitating the transition. However, the molecular mechanisms underlying the silencing of these transcripts remain unclear. In this study, we discovered that activation of lysosomal catabolic activity promotes the exit from the two-cell stage and inhibits the expression of two-cell transcripts. Mechanistically, our research indicates that lysosomal catabolism replenishes intracellular amino acid levels, thereby inactivating transcription factors TFE3/TFEB and suppressing their transcriptional activation of the 2C retrotransposon MERVL/MT2_Mm. Overall, this study reveals the regulatory role of lysosomal activity in the murine embryonic transcriptome and development and uncovers a novel mechanism by which lysosomal signaling controls early embryonic retrotransposon transcription.
Bio:
Fu Xudong is a researcher and doctoral supervisor recognized as a national talent. He obtained his Ph.D. from the University of California, Los Angeles. In 2021, he returned full-time to China as part of the "Hundred Talents Plan" at Zhejiang University. His research focuses on the establishment and regulation of totipotency, stem cell differentiation, and aging through metabolic signaling's impact on the epigenome and transcriptome. His research methods involve multi-omics cross-analysis, relying on cutting-edge technologies such as single-cell sequencing, CRISPR genome screening, metabolic flux measurement, and epigenomic sequencing (Cut&Run, Bisulfite-seq, etc.), combined with bioinformatics analysis to comprehensively investigate related biomedical issues. He has published papers as corresponding or first author in journals such as Nature Cell Biology, Cell Metabolism, Developmental Cell, and Science Advances, and as co-author in academic journals including Nature, Cell Reports, Genes&Development.
