Understanding how cells differentiate during early embryonic development is crucial for advancing regenerative medicine and developmental biology. Pluripotent stem cells (PSCs) have been invaluable tools in this field, as they can transform into various cell types in the body and play key roles during early embryonic development. Unfortunately, research on this topic in humans and other primates has long been hampered by ethical constraints and technical limitations.
Of particular interest are naive-type PSCs, which represent an earlier developmental state than conventional (or 'primed') PSCs and possess enhanced differentiation potential. While human naive PSCs can differentiate into both embryonic and extra-embryonic tissues as the placenta and yolk sac, mouse naive PSCs lack this ability. This raises questions about whether this expanded potential is unique to humans or shared among other primates.
In a groundbreaking study published online in Cell Stem Cell on February 26, 2025 , a research team led by Associate Professor Hideki Masaki from Institute of Science Tokyo, Japan, successfully established cultures of naive-type induced pluripotent stem cells from chimpanzee somatic cells. Not only did they reveal key insights into the mechanisms necessary for self-renewal in these cells but also they became the first in the world to grow chimpanzee blastoids, which are early embryo models, using these cells.
One of the central findings of the study was that inhibiting polycomb repressive complex 2 (PRC2), a protein that can dynamically regulate gene activity and cell differentiation, is necessary for growing chimpanzee naive PSCs. Without this inhibition, the cells failed to propagate despite successful initial reprogramming.
The research team found that chimpanzee naive PSCs share significant similarities with human naive PSCs in terms of gene expression patterns and developmental potential. These cells had the ability to differentiate into trophectoderm and hypoblast, two types of extra-embryonic tissues essential for embryo implantation and development. This capability enabled the researchers to create tri-lineage blastoids containing all three cell types found in very early embryonic development. "Since chimpanzee naive PSCs can transition to multilineage competence or differentiate into other early embryonic tissues, they could provide a higher primate comparative model for studying pluripotency and early embryogenesis," remarks Masaki.
Another significant advancement was the establishment of a feeder-free culture system for naive PSCs. Traditional methods for culturing naive PSCs require a layer of mouse-derived feeder cells. The need for these support cells, even when culturing human PSCs, introduces additional animal components that can complicate potential medical applications. By applying PRC2 inhibitors, the researchers eliminated the need for feeder cells in long-term chimpanzee PSC culture. "Our success in establishing a culturing technique without feeder cells may pave the way to applications in regenerative medicine," notes Masaki.
By establishing that chimpanzee naive PSCs share the expanded differentiation potential observed in human cells, this research sheds light on the evolutionary conservation of these properties. Moreover, the development of chimpanzee blastoid models offers a powerful tool for investigating early developmental processes. As scientists continue to build on these exciting findings, our understanding of embryology across mammals will deepen, potentially leading to advances in regenerative medicine and reproductive biology.
About Institute of Science Tokyo (Science Tokyo)
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of "Advancing science and human wellbeing to create value for and with society."
