(T1203) COMPREHENSIVE ANALYSIS OF DIFFERENTIATION CAPACITY OF EARLY NEUROEPITHELIAL STEM/PROGENITOR CELL LINES DERIVED FROM HUMAN EMBRYONIC BRAIN TISSUE
Postdoctoral Researcher University of Innsbruck Innsbruck, Tirol, Austria
Abstract: Cell lines derived from early embryonic stages have significantly advanced our understanding of mammalian development. However, existing human neural stem/progenitor cell models primarily represent later stages of neurodevelopment, such as rosette-like or radial glial cells, and often fail to maintain long-term clonal self-renewal. Here, we report the successful isolation and establishment of a tissue-derived human neural stem/progenitor cell population that closely mirrors the human neuroepithelium at five weeks of in vivo development. These embryonic neural stem/progenitor cells (eNSPCs) exhibit a distinct naïve, non-polarized, pre-rosette phenotype and demonstrate virtually unlimited self-renewal. Single-cell RNA sequencing revealed that eNSPCs represent a homogeneous population of multipotent stem cells, as opposed to a mixture of committed neural progenitors, with distinctive expression of early neurodevelopmental markers. Notably, this cell population exhibits broad regional plasticity, differentiating into diverse lineages of both the central and peripheral nervous system, including forebrain and midbrain dopaminergic neurons, V2a progenitors, interneurons, and neural crest cells. In conclusion, our findings establish the eNSPC cell population as the earliest stabilized human neural stem/progenitor cell model to date, characterized by broad plasticity, making them an invaluable tool for studying human neurodevelopment and exploring regenerative medicine applications.
