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Recent research has achieved a breakthrough in the cultivation of chimpanzee naive pluripotent stem cells (PSCs) within cellular cultures. In this study, scientists have successfully created models of chimpanzee early embryos, termed ‘blastoids,’ and identified the crucial role of a specific regulatory gene in the self-renewal of chimpanzee PSCs. Furthermore, the researchers have developed a feeder-free culture system, which eliminates the need for mouse-derived feeder cells, thereby enhancing the efficiency of PSC cultivation. These insights present significant implications for the fields of primate embryology, stem cell research, and regenerative medicine.
Grasping the mechanisms behind cell differentiation during early embryonic development is vital for progress in regenerative medicine and developmental biology. Pluripotent stem cells (PSCs) are particularly important as they can differentiate into diverse cell types and are essential during the initial stages of embryonic growth. However, ethical constraints and technical challenges have long hindered research in humans and other primates.
Naive-type PSCs are of special interest as they represent an earlier developmental phase compared to conventional or ‘primed’ PSCs and possess a greater capacity for differentiation. Human naive PSCs can differentiate into both embryonic and extra-embryonic tissues, such as the placenta and yolk sac, while their mouse counterparts do not share this ability. This discrepancy raises questions regarding whether this broader potential is unique to humans or if it is also found in other primates.
A pivotal study published online in Cell Stem Cell on February 26, 2025, led by Associate Professor Hideki Masaki from the Institute of Science in Tokyo, Japan, has successfully established cultures of naive-type induced pluripotent stem cells from chimpanzee somatic cells. This groundbreaking work not only sheds light on the mechanisms vital for self-renewal in these cells but also marks the first instance of growing chimpanzee blastoids using these cells.
A core discovery of the study indicated that inhibiting the polycomb repressive complex 2 (PRC2), a protein that dynamically regulates gene expression and cell differentiation, is essential for the growth of chimpanzee naive PSCs. The absence of this inhibition resulted in a failure to propagate, despite successful reprogramming efforts.
Additionally, the research team observed that chimpanzee naive PSCs exhibited considerable similarities to human naive PSCs in terms of gene expression profiles and differentiation potential. These cells demonstrated the ability to differentiate into trophectoderm and hypoblast, which are crucial extra-embryonic tissues necessary for embryo implantation and development. This capacity enabled the creation of tri-lineage blastoids containing all three essential cell types present in very early embryonic development. “Since chimpanzee naive PSCs can transition to multilineage competence or differentiate into other early embryonic tissues, they could serve as a valuable comparative model among higher primates for the study of pluripotency and early embryogenesis,” noted Masaki.
Another significant achievement was the development of a feeder-free culture system specifically for naive PSCs. Traditional cultivation approaches frequently involve mouse-derived feeder cells, which introduce extraneous biological factors that can complicate medical applications of these cells. By utilizing PRC2 inhibitors, the researchers successfully cultured chimpanzee PSCs without reliance on feeder cells for extended periods. “Our accomplishment in establishing a feeder-free culturing technique may significantly influence future applications in regenerative medicine,” Masaki stated.
This research underscores that chimpanzee naive PSCs retain the extensive differentiation potential observed in human cells, illuminating the evolutionary conservation of these features. Furthermore, the successful creation of chimpanzee blastoid models provides an invaluable resource for exploring the complexities of early developmental processes. As further investigations build on these significant findings, our comprehension of embryology across mammalian species is poised to expand, potentially ushering in innovations in regenerative medicine and reproductive biology.
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