Neuro-mesodermal progenitors (NMPs): a comparative study between pluripotent stem cells and embryo-derived...

Area of Science:

• Developmental biology
• Stem cell research
• Genetics

Background:

• Neural mesodermal progenitors (NMPs) are bipotent stem cells in the mammalian embryo's caudal lateral epiblast (CLE).
• NMPs contribute to spinal cord and paraxial mesoderm formation during axial elongation.
• Current understanding of NMP markers, like Sox2 and T co-expression, is being re-evaluated.

Purpose of the Study:

• To analyze and compare in vitro neural mesodermal progenitor (NMP) populations derived from embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs).
• To compare these in vitro NMP populations with those found in E8.25 mouse CLE.
• To challenge the definition of NMPs based solely on Sox2 and T mRNA co-expression.

Main Methods:

• Single-cell analysis of NMP populations derived from ESCs and EpiSCs.
• Comparison with NMP populations from E8.25 mouse embryos.
• Utilized a support vector machine (SVM) classification model trained on in vivo CLE data to analyze in vitro NMP populations.

Main Results:

• NMP differentiation from ESCs resulted in heterogeneous populations with few cells matching the embryo NMP signature.
• Differentiation from EpiSCs yielded a high proportion of cells with the embryo NMP signature.
• A node-like population within the Epi-NMP source suggests sustained T expression, crucial for NMP generation.

Conclusions:

• Differentiation of EpiSCs into NMPs effectively reproduces in vivo developmental events.
• This suggests a specific sequence for the emergence of NMP populations in vitro.
• The findings challenge the exclusive reliance on Sox2 and T co-expression for defining NMPs.