A Critical Role for Sox9 in Notch-Induced Astrogliogenesis and Stem Cell Maintenance

Martini, Simone; Bernoth, Kristina; Main, Heather; Ortega, Germán Camargo; Lendahl, Urban; Just, Ursula; Schwanbeck, Ralf

doi:10.1002/stem.1320

Cited by 62 publications

(55 citation statements)

References 40 publications

(64 reference statements)

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“…We then carried out SOX9 ChIP-seq in VCaP cells using these two anti-SOX9 antibodies in parallel. Peak calling by the model-based analysis for (-1 kb to +1 kb; -2 kb to +2 kb; -3 kb to +3 kb of TSSs); downstream elements (-1 kb to +1 kb; -2 kb to +2 kb; -3 kb to +3 kb of transcription stop sites); gene body ( 5′UTR, 3′UTR the strongest correlation in both the TCGA and MSKCC data sets, which may in part reflect the reported NOTCH regulation of SOX9 expression (29)(30)(31). The correlation with MAPK signaling may also reflect the reported SOX9 induction through activation of receptor tyrosine kinases, including FGFRs and MET (16,32).…”

Section: Sox9-binding Sites Identified By Chip-seq In Tmprss2:erg Fusmentioning

confidence: 85%

SOX9 drives WNT pathway activation in prostate cancer

Ma¹,

Ye²,

He³

et al. 2016

Journal of Clinical Investigation

148

126

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Section: Sox9-binding Sites Identified By Chip-seq In Tmprss2:erg Fusmentioning

confidence: 85%

SOX9 drives WNT pathway activation in prostate cancer

Ma¹,

Ye²,

He³

et al. 2016

Journal of Clinical Investigation

148

126

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“…The LIF-GST fusion protein was captured with glutathione-Sepharose 4B beads (GE Healthcare, Munich, Germany) and the LIF moiety was released by thrombin cleavage (GE Healthcare). Purity of sterile filtered LIF was checked via Coomassie stained SDS-PAGE, concentration was determined with Bradford assay, and biological activity was tested using Ba/F3-gp130-LIFR cells and mouse ES cell line EB5 [63, 64]. A detailed protocol is available on request.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of protein kinase II (CK2) prevents induced signal transducer and activator of transcription (STAT) 1/3 and constitutive STAT3 activation

et al. 2014

Self Cite

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The Janus kinase / signal transducer and activator of transcription (Jak/STAT) pathway can be activated by many different cytokines, among them all members of the Interleukin (IL-)6 family. Dysregulation of this pathway, resulting in its constitutive activation, is associated with chronic inflammation and cancer development. In the present study, we show that activity of protein kinase II (CK2), a ubiquitously expressed serine/threonine kinase, is needed for induced activation of STAT1 and STAT3 by IL-6 classic and trans-signaling, IL-11, IL-27, oncostatin M (OSM), leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1). Inhibition of CK2 efficiently prevented STAT phosphorylation and inhibited cytokine-dependent cell proliferation in a Jak1-dependent manner. Conversely, forced activation of CK2 alone was not sufficient to induce activation of the Jak/STAT signaling pathway. Inhibition of CK2 in turn inhibited Jak1-dependent STAT activation by oncogenic gp130 mutations. Furthermore, CK2 inhibition diminished the Jak1- and Src kinase-dependent phosphorylation of a constitutively active STAT3 mutant recently described in human large granular lymphocytic leukemia. In conclusion, we characterize CK2 as an essential component of the Jak/STAT pathway. Pharmacologic inhibition of this kinase is therefore a promising strategy to treat human inflammatory diseases and malignancies associated with constitutive activation of the Jak/STAT pathway.

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“…Here we showed that NF‐α1 activated the Raf/MEK/ERK pathway, which then upregulated the expression of Sox9. Sox9 is an important transcription factor that plays a central role in transmitting the signals for major signaling pathways that regulate astrogliogenesis/astrocyte differentiation and its expression could be suppressed by ERK1/2 inhibition . Indeed, we showed that in the presence of the ERK1/2 inhibitor (U0126) and knockdown of Sox9 gene expression by siRNA, NF‐α1 induced GFAP mRNA expression was blocked.…”

Section: Discussionmentioning

confidence: 88%

Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

Selvaraj¹,

Xiao²,

Lee

et al. 2016

Stem Cells

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Embryonic neurodevelopment involves inhibition of proliferation of multipotent neural stem cells followed by differentiation into neurons, astrocytes and oligodendrocytes to form the brain. We have identified a new neurotrophic factor, NF-α1, which inhibits proliferation and promotes differentiation of neural stem cell/progenitors derived from E13.5 mouse cortex. Inhibition of proliferation of these cells was mediated through negatively regulating the Wnt pathway and decreasing β-catenin. NF-α1 induced differentiation of neural stem cells to astrocytes by enhancing Glial Fibrillary Acidic Protein (GFAP) expression through activating the ERK1/2-Sox9 signaling pathway. Cultured E13.5 cortical stem cells from NF-α1-knockout mice showed decreased astrocyte numbers compared to wild-type mice, which was rescued by treatment with NF-α1. In vivo, immunocytochemistry of brain sections and western blot analysis of neocortex of mice showed a gradual increase of NF-α1 expression from E14.5 to P1 and a surge of GFAP expression at P1, the time of increase in astrogenesis. Importantly, NF-α1-KO mice showed ~49% fewer GFAP positive astrocytes in the neocortex compared to WT mice at P1. Thus, NF-α1 is critical for regulating anti-proliferation and cell fate determination, through differentiating embryonic stem cells to GFAP-positive astrocytes for normal neurodevelopment.

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A Critical Role for Sox9 in Notch-Induced Astrogliogenesis and Stem Cell Maintenance

Cited by 62 publications

References 40 publications

SOX9 drives WNT pathway activation in prostate cancer

SOX9 drives WNT pathway activation in prostate cancer

Inhibition of protein kinase II (CK2) prevents induced signal transducer and activator of transcription (STAT) 1/3 and constitutive STAT3 activation

Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment

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