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@ARTICLE{Fukui:139726,
author = {Fukui, Hirokazu and Rünker, Annette and Fabel, Klaus and
Buchholz, Frank and Kempermann, Gerd},
title = {{T}ranscription factor {R}unx1 is pro-neurogenic in adult
hippocampal precursor cells.},
journal = {PLOS ONE},
volume = {13},
number = {1},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DZNE-2020-06048},
pages = {e0190789},
year = {2018},
abstract = {Transcription 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.},
keywords = {Alternative Splicing / Animals / Apoptosis: physiology /
Cell Survival: physiology / Cells, Cultured / Core Binding
Factor Alpha 2 Subunit: genetics / Core Binding Factor Alpha
2 Subunit: metabolism / Dendrites: metabolism / Hippocampus:
cytology / Hippocampus: metabolism / Mice, Inbred C57BL /
Mice, Inbred DBA / Neural Stem Cells: cytology / Neural Stem
Cells: metabolism / Neurogenesis: physiology / Protein
Isoforms / RNA, Messenger: metabolism / Running: physiology
/ Species Specificity / Systems Biology / Transcriptome /
Transfection / Transforming Growth Factor beta1:
administration $\&$ dosage / Transforming Growth Factor
beta1: metabolism / Volition / Core Binding Factor Alpha 2
Subunit (NLM Chemicals) / Protein Isoforms (NLM Chemicals) /
RNA, Messenger (NLM Chemicals) / Runx1 protein, mouse (NLM
Chemicals) / Transforming Growth Factor beta1 (NLM
Chemicals)},
cin = {AG Kempermann 1 / Dresden Pre 2020},
ddc = {610},
cid = {I:(DE-2719)1710001 / I:(DE-2719)6000013},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29324888},
pmc = {pmc:PMC5764282},
doi = {10.1371/journal.pone.0190789},
url = {https://pub.dzne.de/record/139726},
}