Extraembryonic mesoderm cells derived from human embryonic stem cells rely on Wnt pathway activation

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• Extraembryonic mesoderm cells (EXMCs) are crucial for embryonic development and form mesenchymal stem cells (MSCs).
• Generating EXMCs and subsequent MSCs from human primed ESCs (hpESCs) remains a challenge.

Purpose of the Study:

• To establish a protocol for differentiating hpESCs into EXMCs and subsequently into MSCs.
• To characterize the generated EXMCs and MSCs.

Main Methods:

• Utilized a three-dimensional differentiation protocol activating the Wnt pathway in hpESCs.
• Employed single-cell transcriptome and immunostaining analyses for characterization.
• Used cell sorting for purification and expansion of EXMCs.

Main Results:

• Successfully induced hpESCs into EXMCs with characteristics similar to post-implantation EXMCs.
• Generated EXMCs secreted extracellular matrix proteins (e.g., COL3A1) and differentiated into MSCs.
• Derived MSCs showed robust chondrogenic and osteogenic differentiation but lacked adipogenic potential.

Conclusions:

• A novel protocol enables the generation of EXMCs and MSCs from hpESCs.
• The derived MSCs possess distinct differentiation capabilities, highlighting their unique properties.
• This advancement provides a valuable tool for studying early human development and exploring MSC-based therapies.