Dynamics of neuromesodermal progenitors in axial stem cell models

Abstract

This thesis investigates the contribution and regulation of neuromesodermal progenitors (NMPs) during vertebrate axial elongation. Single-cell transcriptomics of human embryos and hPSC-derived axial organoids define NMP identity, lineage contribution, and the roles of WNT, FGF, and TGFβ signaling. Analysis of NMP state transitions further elucidates mechanisms governing NMP maintenance and exit. Finally, human axial stem cells (AxSCs), derived from pluripotent stem cells and exhibiting NMP-like properties, are used to model secondary neurulation in vitro, recapitulating key morphogenetic events including symmetry breaking, mesenchymal-to-epithelial transition, multi-lumen formation, and neural differentiation. Together, this work advances understanding of human NMP biology and provides experimental models for studying axial development and neurulation.

Neuromesodermal progenitorsSecondary neurulationAxial elongationHuman embryonic developmentAxial stem cellsSingle-cell transcriptomicsOrganoids