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000139726 041__ $$aEnglish
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000139726 1001_ $$0P:(DE-2719)9000088$$aFukui, Hirokazu$$b0$$eFirst author
000139726 245__ $$aTranscription factor Runx1 is pro-neurogenic in adult hippocampal precursor cells.
000139726 260__ $$aSan Francisco, California, US$$bPLOS$$c2018
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000139726 520__ $$aTranscription factor Runx1 (Runt Related Transcription Factor 1), plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells. Isoforms 1 and 2 of Runx1 (but not 3 to 5) driven by the proximal promoter were expressed in hippocampal precursor cells ex vivo, albeit again at very low levels, and were markedly increased after stimulation with TGF-β1. Under differentiation conditions (withdrawal of growth factors) Runx1 became down-regulated. Overexpression of Runx1 in vitro reduced proliferation, increased survival of precursor cells by reducing apoptosis, and increased neuronal differentiation, while slightly reducing dendritic morphology and complexity. Transfection with dominant-negative Runx1 in hippocampal precursor cells in vitro did not result in differences in neurogenesis. Hippocampal expression of Runx1 correlated with adult neurogenesis (precursor cell proliferation) across BXD recombinant strains of mice and covarying transcripts enriched in the GO categories 'neural precursor cell proliferation' and 'neuron differentiation'. Runx1 is thus a plausible candidate gene to be involved in regulating initial differentiation-related steps of adult neurogenesis. It seems, however, that the relative contribution of Runx1 to such effect is complementary and will explain only small parts of the cell-autonomous pro-differentiation effect.
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000139726 650_7 $$2NLM Chemicals$$aCore Binding Factor Alpha 2 Subunit
000139726 650_7 $$2NLM Chemicals$$aProtein Isoforms
000139726 650_7 $$2NLM Chemicals$$aRNA, Messenger
000139726 650_7 $$2NLM Chemicals$$aRunx1 protein, mouse
000139726 650_7 $$2NLM Chemicals$$aTransforming Growth Factor beta1
000139726 650_2 $$2MeSH$$aAlternative Splicing
000139726 650_2 $$2MeSH$$aAnimals
000139726 650_2 $$2MeSH$$aApoptosis: physiology
000139726 650_2 $$2MeSH$$aCell Survival: physiology
000139726 650_2 $$2MeSH$$aCells, Cultured
000139726 650_2 $$2MeSH$$aCore Binding Factor Alpha 2 Subunit: genetics
000139726 650_2 $$2MeSH$$aCore Binding Factor Alpha 2 Subunit: metabolism
000139726 650_2 $$2MeSH$$aDendrites: metabolism
000139726 650_2 $$2MeSH$$aHippocampus: cytology
000139726 650_2 $$2MeSH$$aHippocampus: metabolism
000139726 650_2 $$2MeSH$$aMice, Inbred C57BL
000139726 650_2 $$2MeSH$$aMice, Inbred DBA
000139726 650_2 $$2MeSH$$aNeural Stem Cells: cytology
000139726 650_2 $$2MeSH$$aNeural Stem Cells: metabolism
000139726 650_2 $$2MeSH$$aNeurogenesis: physiology
000139726 650_2 $$2MeSH$$aProtein Isoforms
000139726 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000139726 650_2 $$2MeSH$$aRunning: physiology
000139726 650_2 $$2MeSH$$aSpecies Specificity
000139726 650_2 $$2MeSH$$aSystems Biology
000139726 650_2 $$2MeSH$$aTranscriptome
000139726 650_2 $$2MeSH$$aTransfection
000139726 650_2 $$2MeSH$$aTransforming Growth Factor beta1: administration & dosage
000139726 650_2 $$2MeSH$$aTransforming Growth Factor beta1: metabolism
000139726 650_2 $$2MeSH$$aVolition
000139726 7001_ $$0P:(DE-2719)2810792$$aRünker, Annette$$b1
000139726 7001_ $$0P:(DE-2719)2000006$$aFabel, Klaus$$b2
000139726 7001_ $$0P:(DE-HGF)0$$aBuchholz, Frank$$b3
000139726 7001_ $$0P:(DE-2719)2000011$$aKempermann, Gerd$$b4$$eLast author
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