Rat embryonic stem cells produce fertile offspring through tetraploid complementation

Area of Science:

• Stem cell biology
• Developmental biology
• Genetics

Background:

• Embryonic stem cells (ESCs) possess pluripotency, crucial for development.
• Tetraploid complementation is the most rigorous test for assessing ESC pluripotency.
• The ability of non-murine ESCs to pass this test remains largely unexplored.

Purpose of the Study:

• To investigate the developmental potency of rat ESCs using tetraploid complementation.
• To determine if rat ESCs can generate a complete organism.
• To explore the stability of pluripotency in cultured rat ESCs.

Main Methods:

• Derivation of rat ESCs under specific 2i (two small molecule inhibitors) conditions.
• Assessment of pluripotency through tetraploid complementation.
• Analysis of genomic imprinting in cultured rat ESCs.

Main Results:

• Early-passage rat ESCs successfully produced fertile offspring via tetraploid complementation.
• Rat ESCs rapidly lost the capacity for tetraploid complementation upon further culture.
• This loss correlated with a near-complete erasure of genomic imprinting.

Conclusions:

• Naïve ground state pluripotency can be achieved in rat ESCs.
• Species-specific differences exist in the regulation and maintenance of pluripotency.
• Findings have implications for deriving and utilizing naïve pluripotent stem cells in various species, including humans.