TY  - JOUR
AU  - Fukui, Hirokazu
AU  - Rünker, Annette
AU  - Fabel, Klaus
AU  - Buchholz, Frank
AU  - Kempermann, Gerd
TI  - Transcription factor Runx1 is pro-neurogenic in adult hippocampal precursor cells.
JO  - PLOS ONE
VL  - 13
IS  - 1
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2020-06048
SP  - e0190789
PY  - 2018
AB  - 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.
KW  - Alternative Splicing
KW  - Animals
KW  - Apoptosis: physiology
KW  - Cell Survival: physiology
KW  - Cells, Cultured
KW  - Core Binding Factor Alpha 2 Subunit: genetics
KW  - Core Binding Factor Alpha 2 Subunit: metabolism
KW  - Dendrites: metabolism
KW  - Hippocampus: cytology
KW  - Hippocampus: metabolism
KW  - Mice, Inbred C57BL
KW  - Mice, Inbred DBA
KW  - Neural Stem Cells: cytology
KW  - Neural Stem Cells: metabolism
KW  - Neurogenesis: physiology
KW  - Protein Isoforms
KW  - RNA, Messenger: metabolism
KW  - Running: physiology
KW  - Species Specificity
KW  - Systems Biology
KW  - Transcriptome
KW  - Transfection
KW  - Transforming Growth Factor beta1: administration & dosage
KW  - Transforming Growth Factor beta1: metabolism
KW  - Volition
KW  - Core Binding Factor Alpha 2 Subunit (NLM Chemicals)
KW  - Protein Isoforms (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - Runx1 protein, mouse (NLM Chemicals)
KW  - Transforming Growth Factor beta1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29324888
C2  - pmc:PMC5764282
DO  - DOI:10.1371/journal.pone.0190789
UR  - https://pub.dzne.de/record/139726
ER  -