Cell fate commitment is achieved by the establishment of cell type-specific transcriptional programs, which in turn are guided, reinforced, and ultimately locked-in by epigenetic mechanisms. In a new mouse study, scientists at the Australian Regenerative Medicine Institute at Monash University have uncovered that RNA plays a role in the decision-making process in mammalian embryonic development.

The findings are published in Nature Communications in an article titled, “Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo.”

“The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions,” wrote the researchers. “Although, in non-mammalian early embryogenesis, differential RNA localization presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal RNA asymmetries in outer blastomeres of 16-cell stage mouse preimplantation embryos.”

These findings may lead to the development of new regenerative treatments.

“Just a few days into the journey of embryogenesis, when turning into 16 cells, the embryo must make its first difficult decision—which of its cells will give rise to the embryo or will become extra-embryonic tissue, for example, placenta,” explained lead researcher Jennifer Zenker, PhD.

“Ribonucleic acid, RNA, plays a key role here. At the 16-cell stage, the different subtypes of RNA, named rRNAs, mRNAs, and tRNAs, are sorted to the two ends of a cell called apical and basal side. The distribution of RNA subtypes determines what the next generation of cells of the embryo will become,” Zenker said.

While most mRNAs and tRNAs remain parked at the apical side, most rRNA molecules travel down to the basal side on lysosomes.

The crowded basal side, however, is occupied predominantly with rRNAs. Daughter cells obtaining the more active protein factories of the apical side, are more transformable and specialize into the future placenta. The daughter cells which retain their potential to still become any type of cell of the adult organism, called pluripotency, receive the less translationally active bulk of rRNA.

For regenerative medicine, being able to orchestrate cell fate opens up the capacity to generate new stem cell-based treatments for a number of diseases and conditions.

“As in real life, cells can influence the direction of their own future by getting organized early. Our research may open new ways to predict and direct cell fate decisions,” Zenker said.

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