The reporter learned from Shanghai Ocean University that recently, the research team of Professor Chen Liangbiao and Professor Hu Peng has achieved systematic optimization and application of single-cell newborn RNA sequencing technology in live fish embryos, and for the first time, achieved high sensitivity and accuracy detection of newly transcribed genes in the "zygote activation" stage. This technology not only opens a new window for studying the mysteries of the origin of life, but also provides an important tool for precise gene design in aquaculture breeding. When sperm and egg combine, the "book of fate" of the cell opens its first page. However, the vast majority of genes in fertilized eggs are initially 'dormant', and the genes that are quietly 'awakened' at critical moments are the ones that truly determine the course of life - they act as conductors, guiding the entire development process. The beginning of every new life undergoes a "handover" - the transition from genetic material provided by the mother to autonomous control of gene expression by the embryo, a process known as maternal zygotic transition, which is the most critical turning point in embryonic development. However, newly activated zygotic genes have extremely rare transcript quantities and are often "lost" by massive amounts of maternal RNA. This makes it difficult for traditional sequencing techniques to 'hear' these faint but crucial 'sounds'. During his postdoctoral research, Hu Peng participated in the development of cutting-edge single-cell sequencing technology for detecting newly synthesized RNA. In this study, the team systematically optimized the fish embryo model. On the one hand, a systematic evaluation labeling method was implemented, and 10 mainstream RNA chemical transformation methods were systematically screened and tested in over 50000 zebrafish cells. Finally, it was found that the "on beads" conversion scheme based on mCPBA/TFEA can achieve a T-to-C substitution rate of over 8%, which is far superior to traditional "in vivo labeling" methods, and performs excellently in signal intensity and RNA quality. On the other hand, the team accurately labeled newly synthesized RNA by microinjecting 4-thiouridine into the one cell stage of the fertilized egg of zebrafish, a model fish, achieving efficient labeling of zygotic newly transcribed RNA for subsequent identification. It is reported that this study has achieved many breakthroughs. Firstly, the optimized method can clearly capture the signals of new zygotic RNA in the context of massive maternal RNA. Secondly, by calculating the proportion of new RNA, it is possible to accurately determine which genes are activated by embryonic zygotes. Finally, the study identified more previously unreported zygotic activation genes and validated their expression patterns in whole embryos through in situ hybridization experiments. (New Society)