An epiblast stem cell-derived multipotent progenitor population for axial extension

Area of Science:

• Developmental biology
• Stem cell research
• Embryogenesis

Background:

• Mammalian embryos contain bipotent progenitors in the caudal lateral epiblast, known as neural mesodermal progenitors (NMPs).
• NMPs co-express Sox2 and T/brachyury and contribute to spinal cord and paraxial mesoderm development during body axis elongation.
• Current in vitro methods derive NMP-like cells from stem cells, but these lack self-renewal capacity, unlike their embryonic counterparts.

Purpose of the Study:

• To investigate the nature of in vitro derived NMP-like cells.
• To identify a more effective source for multipotent progenitors.
• To characterize the self-renewal and differentiation potential of NMP-like cells derived from epiblast stem cells (EpiSCs).

Main Methods:

• Derivation of NMP-like cells from epiblast stem cells (EpiSCs) in vitro.
• Analysis of cell populations generated by these protocols, including multipotency assessment.
• Gene expression profiling to compare in vitro derived NMP-like cells with embryonic NMPs.
• Investigation of the role of BMP and Nodal signaling in progenitor differentiation.

Main Results:

• In vitro protocols initially yield a multipotent progenitor population, not just NMP-like cells.
• This multipotent population generates NMPs, as well as progenitors for lateral plate and intermediate mesoderm.
• Epiblast stem cells (EpiSCs) are a suitable source for these multipotent progenitors.
• NMP-like cells derived from EpiSCs exhibit limited self-renewal and a gene expression profile similar to embryonic NMPs.
• BMP and Nodal signaling balance is crucial for the differentiation of these progenitors.

Conclusions:

• In vitro derivation protocols produce a transient multipotent progenitor stage before generating NMP-like cells.
• Epiblast stem cells (EpiSCs) provide a valuable source for generating NMP-like cells with characteristics closer to their in vivo counterparts.
• Understanding these progenitor dynamics is key for regenerative medicine and developmental studies.