Key “Missing Link” in Early Mammalian Development Found
Pluripotent cells with Oct1 give rise to cells and tissues of the adult mouse (left, dark color), but fail to without Oct1 (left).
May 30, 2017 12:00 AMA protein called Oct1/Pou2f1 sets the stage for the earliest events that distinguish one type of cell in an embryo from another, U scientists have found. As the development of an embryo, including a human embryo, proceeds, the cells in the embryo begin to take on more and more specific characteristics (this is known as “differentiation”). The new work addresses how mammalian embryos transition from a state that is equally good at forming different cells and tissues (termed “pluripotency”) to the more differentiated state. As cells differentiate and begin to acquire specific characteristics (neurons vs. gut cells for example), Oct1 reinforces those characteristics, and also suppresses the characteristics of other, inappropriate, developmental lineages. Consequently, in the absence of Oct1 differentiating cells are marked not only by the under-expression of developmentally appropriate genes, but also by the abnormal expression of genes for alternate lineages. Oct1 does this by binding to DNA and helping to turn on and off genes specific to different developmental programs.
Work from others had shown that a related protein, Oct4, is important in maintaining pluripotency. The new work set out to address what happens as cells lose pluripotency and begin to differentiate. Oct4 is rapidly lost from these cells, and the new findings show that Oct1 can replace Oct4 at target genes in the early window where cells lose pluripotency and begin to differentiate. “For years, it was assumed that this specific cellular circuitry was simply shut down upon differentiation and loss of Oct4,” says Dr. Dean Tantin, the senior author on the study. “The new work shows that there is more of a continuum. Other activities that are capable of binding the same target genes, such as Oct1, carry at least parts of the program forward through differentiation.”
The studies have broad implications for understanding how different lineages of a developing embryo are specified, and thus are relevant to the field of regenerative medicine, in which using this information specific cell types and organ systems could be better engineered. The work involved investigators in the University of Utah Department of Pathology and Broad Institute of Harvard and MIT. The work was funded by the National Institutes of Health.
Shen Z, Kang J, Shakya A, Tabaka M, Jarboe EA, Regev A, Tantin D. Enforcement of developmental lineage specificity by transcription factor Oct1. (2017) eLife e20937. doi: 10.7554/eLife.20937. You can find the article here.