TY - JOUR
T1 - SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions
AU - Sun, Wei
AU - Cornwell, Adam
AU - Li, Jiashu
AU - Peng, Sisi
AU - Joana Osorio, M.
AU - Aalling, Nadia
AU - Wang, Su
AU - Benraiss, Abdellatif
AU - Lou, Nanhong
AU - Goldman, Steven A.
AU - Nedergaard, Maiken
PY - 2017
Y1 - 2017
N2 - Astrocytes have in recent years become the focus of intense experimental interest, yet markers for their definitive identification remain both scarce and imperfect. Astrocytes may be recognized as such by their expression of glial fibrillary acidic protein, glutamine synthetase, glutamate transporter 1 (GLT1), aquaporin-4, aldehyde dehydrogenase 1 family member L1, and other proteins. However, these proteins may all be regulated both developmentally and functionally, restricting their utility. To identify a nuclear marker pathognomonic of astrocytic phenotype, we assessed differential RNA expression by FACS-purified adult astrocytes and, on that basis, evaluated the expression of the transcription factor SOX9 in both mouse and human brain. We found that SOX9 is almost exclusively expressed by astrocytes in the adult brain except for ependymal cells and in the neurogenic regions, where SOX9 is also expressed by neural progenitor cells. Transcriptome comparisons of SOX9 cells with GLT1 cells showed that the two populations of cells exhibit largely overlapping gene expression. Expression of SOX9 did not decrease during aging and was instead upregulated by reactive astrocytes in a number of settings, including a murine model of amyotrophic lateral sclerosis (SOD1G93A), middle cerebral artery occlusion, and multiple ministrokes. We quantified the relative number of astrocytes using the isotropic fractionator technique in combination with SOX9 immunolabeling. The analysis showed that SOX9 astrocytes constitute 10-20% of the total cell number in most CNS regions, a smaller fraction of total cell number than previously estimated in the normal adult brain.
AB - Astrocytes have in recent years become the focus of intense experimental interest, yet markers for their definitive identification remain both scarce and imperfect. Astrocytes may be recognized as such by their expression of glial fibrillary acidic protein, glutamine synthetase, glutamate transporter 1 (GLT1), aquaporin-4, aldehyde dehydrogenase 1 family member L1, and other proteins. However, these proteins may all be regulated both developmentally and functionally, restricting their utility. To identify a nuclear marker pathognomonic of astrocytic phenotype, we assessed differential RNA expression by FACS-purified adult astrocytes and, on that basis, evaluated the expression of the transcription factor SOX9 in both mouse and human brain. We found that SOX9 is almost exclusively expressed by astrocytes in the adult brain except for ependymal cells and in the neurogenic regions, where SOX9 is also expressed by neural progenitor cells. Transcriptome comparisons of SOX9 cells with GLT1 cells showed that the two populations of cells exhibit largely overlapping gene expression. Expression of SOX9 did not decrease during aging and was instead upregulated by reactive astrocytes in a number of settings, including a murine model of amyotrophic lateral sclerosis (SOD1G93A), middle cerebral artery occlusion, and multiple ministrokes. We quantified the relative number of astrocytes using the isotropic fractionator technique in combination with SOX9 immunolabeling. The analysis showed that SOX9 astrocytes constitute 10-20% of the total cell number in most CNS regions, a smaller fraction of total cell number than previously estimated in the normal adult brain.
KW - Astrocyte marker
KW - Astrocytes
KW - SOX9
KW - Transcriptome
U2 - 10.1523/jneurosci.3199-16.2017
DO - 10.1523/jneurosci.3199-16.2017
M3 - Journal article
C2 - 28336567
AN - SCOPUS:85019076649
SN - 0270-6474
VL - 37
SP - 4493
EP - 4507
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 17
ER -