An alternative pluripotent state confers interspecies chimaeric competency.

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Regenerative Medicine

Background:

• Pluripotency is the ability of embryonic cells to generate any cell type.
• Existing embryonic stem cells and epiblast stem cells represent limited temporal states of pluripotency.
• Ontogenesis is a dynamic process, suggesting a broader spectrum of pluripotency may exist.

Purpose of the Study:

• To identify and characterize novel pluripotent stem cell types beyond established embryonic and epiblast stem cells.
• To explore the potential of these new stem cells in regenerative medicine and developmental studies.
• To investigate the possibility of capturing different spatial and temporal states of pluripotency.

Main Methods:

• Modulating culture parameters to derive new stem cell types from mouse embryos and primate pluripotent stem cells.
• Characterizing the unique spatial, molecular, and functional features of the derived stem cells.
• Assessing the potential of human rsPSCs in generating interspecies chimaeric embryos.

Main Results:

• Efficiently obtained a novel stem cell type, region-selective pluripotent stem cells (rsPSCs), from mouse embryos and primate pluripotent stem cells, including human cells.
• rsPSCs exhibit unique spatial characteristics and distinct molecular and functional properties.
• Human rsPSCs are easily cultured, genome-edited, and can generate post-implantation interspecies chimaeric embryos.

Conclusions:

• Region-selective pluripotent stem cells (rsPSCs) represent a previously unrecognized state of organismal pluripotency.
• Human rsPSCs hold significant promise for regenerative medicine due to their ease of manipulation and unique developmental potential.
• The ability of human rsPSCs to form chimaeras may advance the understanding of early human development and evolution.