SOX2, a Persistent Marker for Multipotential Neural Stem Cells Derived from Embryonic Stem Cells, the Embryo or the Adult

TLDR

Multipotent neural stem cells are present throughout CNS development, persist into adulthood in defined regions, and can be derived from embryonic stem cells. Transgenic mice were created expressing EGFP under the endogenous Sox2 locus to prospectively identify neural stem/progenitor cells in vivo and in vitro. SOX2 is expressed in multipotent neural stem cells at all stages of mouse ontogeny, and EGFP reporter mice show that SOX2‑positive cells proliferate across the CNS, form self‑renewing neurospheres that differentiate into neurons, astrocytes, and oligodendrocytes, establishing SOX2 as a universal neural stem cell marker.

Abstract

Multipotent neural stem cells are present throughout the development of the central nervous system (CNS), persist into adulthood in defined locations and can be derived from more primitive embryonic stem cells. We show that SOX2, an HMG box transcription factor, is expressed in multipotent neural stem cells at all stages of mouse ontogeny. We have generated transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the endogenous locus-regulatory regions of the <i>Sox2</i> gene to prospectively identify neural stem/progenitor cells in vivo and in vitro. Fluorescent cells coexpress SOX2 protein, and EGFP fluorescence is detected in proliferating neural progenitor cells of the entire anterior-posterior axis of the CNS from neural plate stages to adulthood. SOX2-EGFP cells can form neurospheres that can be passaged repeatedly and can differentiate into neurons, astrocytes and oligodendrocytes. Moreover, prospective clonal analysis of SOX2- EGFP-positive cells shows that all neurospheres, whether isolated from the embryonic CNS or the adult CNS, express SOX2-EGFP. In contrast, the pattern of SOX2-EGFP expression using randomly integrated <i>Sox2</i> promoter/reporter construct differs, and neurospheres are heterogeneous for EGFP expression. These studies demonstrate that SOX2 may meet the requirements of a universal neural stem cell marker and provides a means to identify cells which fulfill the basic criteria of a stem cell: self-renewal and multipotent differentiation.