Primed human pluripotent stem cell-derived blastocyst-like cell aggregates with partial lineage specification

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Biomaterials Science

Background:

• Human blastoids are crucial for studying early human development.
• Current methods use naïve human pluripotent stem cells (hPSCs), which are chromosomally unstable and difficult to handle.

Purpose of the Study:

• To develop an accessible method for generating human blastocyst-like structures from primed hPSCs.
• To evaluate the morphological, molecular, and functional characteristics of these blastoid models.

Main Methods:

• Utilized a thermoresponsive hydrogel to aggregate primed hPSCs.
• Assessed blastoid morphology, lineage marker expression (immunocytochemistry), transcriptional profiles (single-cell RNA sequencing), and in vitro implantation capacity.

Main Results:

• Generated blastoid aggregates mimicked human blastocyst morphology and key lineage markers (epiblast, trophectoderm, primitive endoderm).
• Single-cell RNA sequencing showed a subset of cells with relevant transcriptional profiles, though some remained undifferentiated.
• Blastoids exhibited in vitro implantation potential, trophoblast differentiation, and human chorionic gonadotropin secretion.

Conclusions:

• Introduced a more accessible platform for generating human blastoid models from primed hPSCs.
• These blastoids enhance the study of early human development, early-onset diseases, regenerative medicine, and assisted reproductive technologies.