Pax6 promotes neurogenesis in human neural stem cells

Kallur, Therése; Gisler, Ramiro; Lindvall, Olle; Kokaia, Zaal

doi:10.1016/j.mcn.2008.05.010

Cited by 44 publications

(33 citation statements)

References 64 publications

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“…Other probes which present an upregulation trend that we would like to highlight are BCL2 [493], [494], FYCO1 [495], [496], PAX6 [111], [497], [498], [499] (Figure 17), and QKI [500] (Figure 18). The increase of expression of these probes, together with SOX2, is intriguing as they are related to differentiation from stem cells and are considered critical in neurogenesis [501], [502], [503], [504], [505], [506], [507], [508], [509], [510].…”

Section: Resultsmentioning

confidence: 95%

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

et al. 2010

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BackgroundAlzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive.Methodology/Principal FindingsWe have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity.Conclusions/SignificanceA transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation.

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Section: Resultsmentioning

confidence: 95%

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

et al. 2010

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“…We started with Pax6, a highly conserved transcription factor which is a potential key regulator of neuronal cell fate choice (Kallur, et al, 2008). Western blots were used to quantify Pax6 protein levels in SVZ tissues isolated immediately following AIH treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…One candidate gene is paired box gene 6 (Pax6). Pax6 is a well-conserved transcription factor with an established role in sensory organ development, and is also a potential key regulator of neuronal cell fate choice (Kallur, et al, 2008). Western blotting results showed a moderate elevation of Pax6 protein levels in SVZ tissues isolated immediately following AIH treatments (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

In vivo intermittent hypoxia elicits enhanced expansion and neuronal differentiation in cultured neural progenitors

Ross

Sandhu

Cheung

et al. 2012

Experimental Neurology

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In vitro exposure of neural progenitor cell (NPC) populations to reduced O2 (e.g. 3% versus 20%) can increase their proliferation, survival and neuronal differentiation. Our objective was to determine if an acute (<1 hr), in vivo exposure to intermittent hypoxia (AIH) alters expansion and/or differentiation of subsequent in vitro cultures of NPC from the subventricular zone (SVZ). Neonatal C57BL/6 mice (postnatal day 4) were exposed to an AIH paradigm (20×1 minute; alternating 21% and 10% O2). Immediately after AIH, SVZ tissue was isolated and NPC populations were cultured and assayed either as neurospheres (NS) or as adherent monolayer cells (MASC). AIH markedly increased the capacity for expansion of cultured NS and MASC, and this was accompanied by increases in a proliferation maker (Ki67), MTT activity and hypoxia-inducible factor-1α (HIF-1α) signaling in NS cultures. Peptide blockade experiments confirmed that proteins downstream of HIF-1α are important for both proliferation and morphological changes associated with terminal differentiation in NS cultures. Finally, immunocytochemistry and Western blotting experiments demonstrated that AIH increased expression of the neuronal fate determination transcription factor Pax6 in SVZ tissue, and this was associated with increased neuronal differentiation in cultured NS and MASC. We conclude that in vivo AIH exposure can enhance the viability of subsequent in vitro SVZ-derived NPC cultures. AIH protocols may therefore provide a means to “prime” NPC prior to transplantation into the injured central nervous system.

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“…Recent work demonstrates that GABAergic inhibitory interneurons can be efficiently derived from mouse or human ES cells and fetal cortical neural progenitors by different approaches (Aubry et al, 2008; Bosch et al, 2004; Chatzi et al, 2009; Erceg et al, 2008; Kallur et al, 2008; Kitazawa and Shimizu, 2007; Laeng et al, 2004; Sarichelou et al, 2008; Spiliotopoulos et al, 2009). These promising findings suggest that GABA cell therapy may be possible in patients with neurodegenerative disorders or epilepsy; however, successful cell replacement therapy for these patients may require replacing specific types of GABAergic neurons.…”

Section: Interneuron Diversity and Vulnerability In Epilepsymentioning

confidence: 99%

Recent advancements in stem cell and gene therapies for neurological disorders and intractable epilepsy

et al. 2010

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The potential applications of stem cell therapies for treating neurological disorders are enormous. Many laboratories are focusing on stem cell treatments for CNS diseases, including spinal cord injury, Amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, stroke, traumatic brain injury, and epilepsy. Among the many stem cell types under testing for neurological treatments, the most common are fetal and adult brain stem cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. An expanding toolbox of molecular probes is now available to allow analyses of neural stem cell fates prior to and after transplantation. Concomitantly, protocols are being developed to direct the fates of stem cell derived neural progenitors, and also to screen stem cells for tumorigenicity and aneuploidy. The rapid progress in the field suggests that novel stem cell and gene therapies for neurological disorders are in the pipeline.

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Pax6 promotes neurogenesis in human neural stem cells

Cited by 44 publications

References 64 publications

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

In vivo intermittent hypoxia elicits enhanced expansion and neuronal differentiation in cultured neural progenitors

Recent advancements in stem cell and gene therapies for neurological disorders and intractable epilepsy

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