Chimpanzee Stem Cells Offer New Insights into Early Embryonic Development

Chimpanzee naive pluripotent stem cells (PSCs) can now be grown in cellular cultures, reveals a recent study. They successfully created chimpanzee early embryo models, called ‘blastoids,’ and found that the inhibition of a specific regulatory gene is essential for chimpanzee PSC self-renewal. They also developed a feeder-free culture system, eliminating the need for mouse-derived feeder cells as support. These findings provide valuable insights into primate embryology and could advance stem cell research and regenerative medicine.

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.

Authors:

Tao Huang¹, Arthur Radley^1,13, Ayaka Yanagida^2,3, Zhili Ren¹, Francesca Carlisle¹, Somayyeh Tahajjodi¹, Dongwan Kim⁴, Paul O’Neill⁵, James Clarke^6,14, Madeline A. Lancaster⁷, Zoe Heckhausen^8,9, Jingran Zhuo¹⁰, João Pedro Agostinho de Sousa¹⁰, Petra Hajkova^8,9, Ferdinand von Meyenn¹⁰, Hiroo Imai¹¹, Hiromitsu Nakauchi^3,4,12, Ge Guo¹, Austin Smith*¹, and Hideki Masaki*^3,4

Title:

Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee

Journal:

Cell Stem Cell

DOI:

10.1016/j.stem.2025.02.002

Affiliations:

¹Living Systems Institute, University of Exeter, UK
²Department of Veterinary Anatomy, The University of Tokyo, Japan
³Division of Stem Cell Therapy, Institute of Medical Science, University of Tokyo, Japan
⁴Stem Cell Therapy Division, Institute of Integrated Research, Institute of Science Tokyo, Japan
⁵University of Exeter Sequencing Facility, University of Exeter, UK
⁶Wellcome-MRC Stem Cell Institute, University of Cambridge, UK
⁷MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, UK
⁸MRC Laboratory of Medical Sciences (LMS), UK
⁹Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, UK
¹⁰Department of Health Sciences and Technology, ETH Zurich, Switzerland
¹¹Department of Cellular and Molecular Biology, Center for the Evolutionary Origins of Human Behavior, Kyoto University, Japan
¹²Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, USA

• Successful generation of functional parathyroid glands from mouse embryonic stem cells | Former TMDU

• Hideki Masaki | Science Tokyo Research Information DB
• Kim Dongwan | Science Tokyo Research Information DB
• Stem Cell Therapy Laboratory
• Institute of Integrated Research