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Forschungsdatenbank PMU-SQQUID

TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons.
Kandasamy, M; Lehner, B; Kraus, S; Sander, PR; Marschallinger, J; Rivera, FJ; Trümbach, D; Ueberham, U; Reitsamer, HA; Strauss, O; Bogdahn, U; Couillard-Despres, S; Aigner, L;
J Cell Mol Med. 2014; 18(7):1444-1459
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Couillard-Després Sébastien
Marschallinger Julia
Reitsamer Herbert
Rivera Gomez-Barris Francisco J.

Abstract

Members of the transforming growth factor (TGF)-β family govern a wide range of mechanisms in brain development and in the adult, in particular neuronal/glial differentiation and survival, but also cell cycle regulation and neural stem cell maintenance. This clearly created some discrepancies in the field with some studies favouring neuronal differentiation/survival of progenitors and others favouring cell cycle exit and neural stem cell quiescence/maintenance. Here, we provide a unifying hypothesis claiming that through its regulation of neural progenitor cell (NPC) proliferation, TGF-β signalling might be responsible for (i) maintaining stem cells in a quiescent stage, and (ii) promoting survival of newly generated neurons and their functional differentiation. Therefore, we performed a detailed histological analysis of TGF-β1 signalling in the hippocampal neural stem cell niche of a transgenic mouse that was previously generated to express TGF-β1 under a tetracycline regulatable Ca-Calmodulin kinase promoter. We also analysed NPC proliferation, quiescence, neuronal survival and differentiation in relation to elevated levels of TGF-β1 in vitro and in vivo conditions. Finally, we performed a gene expression profiling to identify the targets of TGF-β1 signalling in adult NPCs. The results demonstrate that TGF-β1 promotes stem cell quiescence on one side, but also neuronal survival on the other side. Thus, considering the elevated levels of TGF-β1 in ageing and neurodegenerative diseases, TGF-β1 signalling presents a molecular target for future interventions in such conditions.


Useful keywords (using NLM MeSH Indexing)

Animals

Biomarkers/metabolism

Blotting, Western

Cell Aging

Cell Differentiation*

Cell Proliferation

Cells, Cultured

Electrophysiology

Female

Gene Expression Profiling

Hippocampus/cytology*

Hippocampus/metabolism

Humans

Mice

Mice, Transgenic

Neurogenesis/physiology*

Neurons/cytology*

Neurons/metabolism

Oligonucleotide Array Sequence Analysis

RNA, Messenger/genetics

Rats

Rats, Inbred F344

Real-Time Polymerase Chain Reaction

Reverse Transcriptase Polymerase Chain Reaction

Stem Cell Niche*

Stem Cells/cytology*

Stem Cells/metabolism

Transforming Growth Factor beta/genetics

Transforming Growth Factor beta/metabolism*


Find related publications in this database (Keywords)

TGF-1
Smad2
stem cells
cell cycle
doublecortin
differentiation