Researchers Find Key Signal Regulating Earliest Stages of Mammalian Development

To develop stem cell therapies, scientists must often “reprogram” specialized body cells like skin cells or blood cells to an earlier, more generalist state. Both reprogramming and body development hinge on the precise levels of a gene called Oct4. Oct4 prevents cells in early embryos from specializing too soon and helps reprogram older cells to act like stem cells—but if there’s too much or too little Oct4, cells will become specialized.

What controls Oct4 levels in early development, and how to replicate that control to “wind back the clock” and revert cells to stem-cell-like states, were unknown.

Now, researchers at the University of Utah Health have uncovered how Oct4 levels are regulated to promote an unspecialized, stem-cell-like state, shedding light on the earliest stages of vertebrate development and opening doors to better stem cell therapies. The scientists pinpointed a region of Oct4 that interacts with DNA and reacts to a type of chemical signaling called oxidation signaling, which tunes down Oct4 activity.

The researchers found that preventing that fine-tuning process interferes with cells’ progression to more specialized states and is vital to early stages of development in mice. “Our results open up the possibility of controlling the reprogramming process better for regenerative medicine and disease modeling,” said Dean Tantin, PhD, senior author on the study.

The paper published in Genes & Development on May 7, 2024.