Chicken Interspecies Chimerism Unveils Human Pluripotency

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Comparative Biology

Background:

• Human pluripotent stem cells (hPSCs) exist in primed and naive states, with distinct properties.
• Assessing the developmental potential of naive vs. primed hPSCs in vivo has been challenging due to a lack of suitable animal models.
• Understanding these differences is crucial for regenerative medicine and developmental studies.

Purpose of the Study:

• To establish a novel animal model for evaluating the pluripotency of human pluripotent stem cells (hPSCs).
• To compare the chimera formation potential of naive-like and primed hPSCs in a developing host.
• To determine the influence of developmental stage matching on hPSC contribution to embryogenesis.

Main Methods:

• Transplantation of naive-like and primed hPSCs into developing chicken embryos at matched and non-matched developmental stages.
• Analysis of robust chimerism to assess pluripotency potential.
• Comparative evaluation of chimera formation efficiency based on hPSC state and injection timing.

Main Results:

• Developing chicken embryos serve as a permissive host for both naive-like and primed hPSCs, supporting robust chimerism.
• Naive-like hPSCs showed significantly reduced chimera formation when injected at non-matched developmental stages compared to primed hPSCs.
• Primed hPSCs maintained consistent chimera formation regardless of developmental stage matching.

Conclusions:

• The developing chicken embryo is a versatile and informative host for assessing the pluripotency of different human pluripotent stem cell states.
• Developmental stage compatibility is critical for naive hPSC contribution to embryogenesis, but less so for primed hPSCs.
• This chick embryo model offers a valuable platform for future studies on hPSC developmental potential and comparative pluripotency.