RNA sequestration in P-bodies directs cell fate transitions

A new study published in Natural biotechnology shows that stem cell differentiation is linked to cellular structures called P-bodies, providing a potential means of controlling cellular identity. Researchers from Baylor College of Medicine, University of Colorado Boulder and collaborating institutions studied P-bodies at different developmental stages in several vertebrate species and found that selective RNA sequestration directs cell fate transitions.

“Our work shows that P-bodies sequester RNAs encoding key proteins related to cell fate to prevent their translation. These RNAs are often characteristic of a previous developmental stage, and in some cases the release of these RNAs is sufficient to drive cellular identity at that earlier developmental stage. Exploiting this regulatory mechanism allows the generation of clinically relevant cell types that would otherwise be difficult to get,” said co-corresponding author Dr. Justin Brumbaugh. assistant professor of molecular, cellular, and developmental biology at the University of Colorado Boulder.

“By manipulating P-body assembly, we can direct pluripotent stem cells toward clinically relevant cell types, such as primordial germ cells and totipotent-like cells. Primordial germ cells are the precursors to sperm and eggs, providing a valuable model for studying infertility and lineage biology germinal. “Totipotent-like cells open new avenues for regenerative medicine and for understanding the early stages of embryonic development,” said the co-correspondent. author Dr. Bruno Di Stefano, assistant professor of molecular and cellular biology at Baylor’s Center for Stem Cells and Regenerative Medicine. Di Stefano is also a CPRIT Cancer Research Fellow and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

The researchers also noted that their analyzes suggest that non-coding RNAs called microRNAs help drive RNA sequestration in P-bodies. According to Di Stefano, microRNA modulation could allow RNA-based therapeutic strategies to control which RNAs are stored in P-bodies and guide cellular identity.