A new study published in Nature Biotechnology shows that stem cell differentiation is linked to cellular structures called P-bodies, providing a potential means of controlling cell identity. Researchers at Baylor College of Medicine, the University of Colorado Boulder and collaborating institutions studied P-bodies in various developmental stages across multiple vertebrate species and found that selective RNA sequestration directed cell fate transitions.
"Our work shows that P-bodies sequester RNAs encoding key cell fate-related proteins to prevent their translation. These RNAs are often characteristic of a preceding developmental stage, and in some cases, releasing these RNAs is sufficient to drive cell identity to that earlier developmental stage. Leveraging this regulatory mechanism permits the generation of clinically relevant cell types that are otherwise difficult to obtain," 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 of sperm and eggs, providing a valuable model for studying infertility and germline biology. Totipotent-like cells open new avenues for regenerative medicine and for understanding the earliest stages of embryonic development," said co-corresponding author Dr. Bruno Di Stefano, assistant professor of molecular and cellular biology in the Stem Cell and Regenerative Medicine Center at Baylor. Di Stefano also is a CPRIT Scholar in cancer research and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.
Researchers also noted that their analyses suggests that noncoding RNAs called microRNAs help drive RNA sequestration into P-bodies. According to Di Stefano, modulating microRNAs may enable RNA-based therapeutic strategies to control which RNAs are stored in P-bodies and guide cell identity.
