SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions

Wei Sun; Adam Cornwell; Jiashu Li; Sisi Peng; M. Joana Osorio; Nadia Aalling; Su Wang; Abdellatif Benraiss; Nanhong Lou; Steven A. Goldman; Maiken Nedergaard

doi:10.1523/jneurosci.3199-16.2017

SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions

Wei Sun^*, Adam Cornwell, Jiashu Li, Sisi Peng, M. Joana Osorio, Nadia Aalling, Su Wang, Abdellatif Benraiss, Nanhong Lou, Steven A. Goldman, Maiken Nedergaard

^*Corresponding author for this work

92 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Neuroscience
Volume	37
Issue number	17
Pages (from-to)	4493-4507
Number of pages	15
ISSN	0270-6474
DOIs	https://doi.org/10.1523/jneurosci.3199-16.2017
Publication status	Published - 2017

Keywords

Astrocyte marker
Astrocytes
SOX9
Transcriptome

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title = "SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions",

abstract = "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.",

keywords = "Astrocyte marker, Astrocytes, SOX9, Transcriptome",

author = "Wei Sun and Adam Cornwell and Jiashu Li and Sisi Peng and {Joana Osorio}, M. and Nadia Aalling and Su Wang and Abdellatif Benraiss and Nanhong Lou and Goldman, {Steven A.} and Maiken Nedergaard",

year = "2017",

doi = "10.1523/jneurosci.3199-16.2017",

language = "English",

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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

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AN - SCOPUS:85019076649

SN - 0270-6474

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SP - 4493

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JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

IS - 17

ER -

SOX9 is an astrocyte-specific nuclear marker in the adult brain outside the neurogenic regions

Abstract

Keywords

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