Assessing the bipotency of in vitro-derived neuromesodermal progenitors

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Genetics

Background:

• Mouse studies reveal a common bipotent progenitor for spinal cord neurectoderm and paraxial mesoderm: neuromesodermal progenitors (NMPs).
• NMPs co-express T(Brachyury) (T(Bra)) and Sox2, crucial for embryonic axial structure development.
• NMP-like cells are generated in vitro from pluripotent stem cells via Wnt and FGF signaling.

Purpose of the Study:

• To determine if single, in vitro-derived NMP-like cells can produce both neural and mesodermal progeny.
• To investigate the bipotency of NMP-like cells generated from mouse epiblast stem cells (EpiSCs).

Main Methods:

• Culture of mouse epiblast stem cells (EpiSCs) under conditions inducing NMP formation.
• Stimulation with combined Wnt and fibroblast growth factor (FGF) signaling.
• Analysis of clonal progeny from T(Bra)-positive cells to assess neural and mesodermal differentiation capacity.

Main Results:

• In vitro-derived T(Bra)-positive cells from EpiSCs generated both neural and mesodermal clones.
• This demonstrates that individual in vitro-derived NMP-like cells are bipotent, capable of producing both cell types.
• The in vitro system recapitulates the bipotency observed in embryonic NMPs.

Conclusions:

• In vitro-derived NMP-like cells are truly bipotent, similar to their in vivo counterparts.
• These cells serve as a valuable model for studying the molecular mechanisms underlying developmental cell fate decisions.
• The findings advance our understanding of neural and mesodermal lineage development from pluripotent stem cells.