Sox2 expression defines a heterogeneous population of neurosphere-forming cells in the adult murine brain.
The identification of neural stem cells (NSCs) in situ has been prevented by the inability to identify a marker consistently expressed in all adult NSCs and is thus generally accomplished using the in vitro neurosphere-forming assay. The high-mobility group transcription factor Sox2 is expressed in embryonic neural epithelial stem cells; because these cells are thought to give rise to the adult NSC population, we hypothesized that Sox2 may continue to be expressed in adult NSCs. Using Sox2:EGFP transgenic mice, we show that Sox2 is expressed in neurogenic regions along the rostral-caudal axis of the central nervous system throughout life. Furthermore, all neurospheres derived from these neurogenic regions express Sox2, suggesting that Sox2 is indeed expressed in adult NSCs. We demonstrate that NSCs are heterogeneous within the adult brain, with differing capacities for cell production. In vitro, all neurospheres express Sox2, but the expression of markers common to early progenitor cells within individual neurospheres varies; this heterogeneity of NSCs is mirrored in vivo. For example, both glial fibrillary acidic protein and NG2 are expressed within individual neurospheres, but their expression is mutually exclusive; likewise, these two markers show distinct staining patterns within the Sox2+ regions of the brain's neurogenic regions. Thus, we propose that the expression of Sox2 is a unifying characteristic of NSCs in the adult brain, but that not all NSCs maintain the ability to form all neural cell types in vivo.
Brazel
Christine Y
CY
Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
Limke
Tobi L
TL
Osborne
Jihan K
JK
Miura
Takumi
T
Cai
Jingli
J
Pevny
Larysa
L
Rao
Mahendra S
MS
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D024002:HMGB Proteins / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D019098:Telomerase