Source: Michigan State University, Justin Whitmore
Michigan State University researcher Jason Knott contributed his expertise in the field of embryo and cellular development to the journal Nature Structural and Molecular Biology (NSMB) to review two recent lab discoveries related to research conducted in Knott’s lab.
Knott, professor in the MSU Department of Animal Science, leads a National Institute of Health (NIH) funded project that is examining how transcription factor AP2 gamma (TFAP2C) regulates trophoblast lineage formation in mammals. While working on this project his research team made an unexpected discovery.
Although, TFAP2C is a well-established regulator of the trophoblast lineage, Knott and his team found that TFAP2C also regulates the activation of pluripotency genes in the preimplantation embryo. Pluripotency genes are necessary for formation of the embryo proper that gives rise to the approximately 200 different cell-types in the developing fetus.
Understanding proper lineage formation in preimplantation embryos may allow researchers to identify future abnormalities in cell development. This discovery is relevant to assisted reproductive technologies (ART), cellular reprogramming, and learning more about pregnancy complications that may originate in the preimplantation embryo.
Knott’s ongoing research prompted NSMB to seek his input on related work by researchers from the University of Cambridge in the United Kingdom and Tsinghua University in Beijing, China. Knott and his research team, consisting of post-doctoral scientist Jaehwan Kim and graduate student Chad Driscoll, authored the article to provide context on the findings and insight into future questions these findings present.
Early embryonic cells begin as ‘totipotent’ – meaning they are yet to be defined and have the capacity to give rise to all cells in the embryo and the future fetus and placenta. Between the 2–cell and the early 8–cell stage, totipotency is progressively lost and replaced with a bipotent state, meaning the cells can develop into only two types of cells, the pluripotent inner cells and the outer trophoblast cells. By the 8-cell stage the shift from totipotent to bipotent cells is complete.
The two articles in Nature Structural & Molecular Biology provide clues into the process of how early embryos switch from a totipotent state to a transitional ‘bipotent state’ to prepare for the first cell-fate decision, Knott and his team said. Three genes were shown to regulate this bipotent state, including TFAP2C. Knott and his research team are scheduled to publish their most recent findings on the role of TFAP2C in pluripotency in 2025.
“Dairy cattle and humans struggle a lot with fertility issues and this discovery will provide new insights into potential embryonic origins,” Knott said. “This work helps us further understand the mechanisms that control formation of early cell lineages, which is critical for a healthy pregnancy. Proper formation of the trophoblast lineage, which makes the placenta, and accurate establishment of the pluripotent inner cells that make the fetus, are the foundation for healthy pregnancy.”
Knott is a member of the MSU Reproductive and Developmental Sciences Training Program, which trains young scientists to pursue research in high priority topic areas identified by the National Institute of Child Health and Human Development (NICHD). Knott’s research team collaborates with professors Keith Latham (Animal Science) and Amy Ralston (Biochemistry and Molecular Biology) at MSU.
