SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult.
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 Sox2 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 Sox2 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.
Ellis
Pam
P
Neuroscience Center, Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Fagan
B Matthew
BM
Magness
Scott T
ST
Hutton
Scott
S
Taranova
Olena
O
Hayashi
Shigemi
S
McMahon
Andrew
A
Rao
Mahendra
M
Pevny
Larysa
L
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002678:Chimera; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D024002:HMGB Proteins; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055748:SOXB1 Transcription Factors; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D009687:Nuclear Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins