Generating Human Blastoids Following Transient Naïve Resetting of Primed Pluripotent Stem Cells

Area of Science:

• Stem cell biology
• Developmental biology
• Reproductive medicine

Background:

• Human pluripotent stem cells (hPSCs) exist in naïve and primed pluripotency states.
• Naïve hPSCs can form blastocysts but are prone to genetic/epigenetic instability, impacting blastoid quality.
• Existing methods for generating human blastoids often rely on these unstable naïve hPSC cultures.

Purpose of the Study:

• To develop an optimized protocol for generating high-quality human blastoids.
• To address the instability issues associated with naïve human pluripotent stem cells.
• To provide a robust method for blastoid formation directly from primed hPSCs.

Main Methods:

• A transient resetting method to convert primed hPSCs into a stable naïve-like state.
• Culturing converted cells to form human blastoids.
• Compatibility assessment with feeder-free and feeder-based culture systems.

Main Results:

• Successfully generated human blastoids directly from primed hPSCs using the transient resetting method.
• The protocol overcomes the limitations of unstable naïve hPSC cultures.
• Demonstrated high efficiency and robustness in blastoid formation.

Conclusions:

• Transient resetting offers a reliable strategy for generating stable human blastoids.
• This advancement improves the developmental potential and quality of hPSC-derived blastoids.
• The protocol is adaptable to different culture conditions, enhancing its utility.