Some mammals can hit pause on a pregnancy, and understanding how that happens could help us treat cancer, researchers report.
Seals give birth onyl when conditions are right. After mating, a female seal can delay implantation of the embryo in the uterine wall-pausing pregnancy until she senses that her fat reserves align with the season. This strategy, known as embryonic diapause, is practiced by hundreds of mammals, from mice to moose. But how does an embryo, built to follow a strict developmental schedule, seamlessly halt and restart?
Now, a new study in Genes & Progress reveals how diapaused embryonic stem cells of mice maintain their ability to become any cell type.
Whether due to insufficient nutrients or the absence of key growth signals, these cells consistently activated the same built-in brake: a molecular program that switches off pathways that normally push cells to differentiate.
This newly discovered mechanism may explain not only how embryos thrive after diapause, but also how certain immune cells-and even cancer cells-can survive long periods of metabolic stress.
“The study of diapause is exciting,because we’re dealing with the ultimate survival strategy,” says Alexander Tarakhovsky,head of the Laboratory of Immune Cell Epigenetics and Signaling at Rockefeller University.
“Our work explains how these cells enter suspended animation, which should derail the developmental schedule, yet still become normal embryos that give rise to normal animals.”
Embryonic diapause is widespread throughout the animal kingdom, with mammals, fish, insects, and many species making use of the same basic strategy. (Humans are an exception.) In mammals, development generally pauses at the blastocyst stage, shortly after fertilization, when the embryo is a ball of a few hundred cells. The blastocyst remains in limbo until conditions improve, upon which it implants in the uterine wall and proceeds to grow as usual.
Prior studies have shown that embryonic stem cells can slip into a diapause-like state of suspended animation in the lab when exposed to different forms of stress.Blocking mTOR (a regulator of cellular growth and metabolism) shuts down the pathways that build proteins and other components, leading to diapause; reducing Myc family transcription factors (master switches that drive cell growth programs) quiets the gene-expression programs needed for rapid growth, and altering chromatin regulators such as MOF likewise pushes cells into a low-energy mode. The fact that such distinct disruptions all led to diapause-like conditions led researchers to view this state as a sort of protective default.
“Diapause appears to be a state that can be reached in many different ways and due to many different kinds of harsh circumstances,” Tarakhovsky says. “Imagine that citizens of a city all evacuate, but for different reasons.One has no food, one has no water, the other has noisy neighbors. They all leave the city, but the pathway leading up to leaving…
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