Article (Scientific journals)
A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1-miRNA feedback loop.
Palm, Thomas; Hemmer, Kathrin; Winter, Julia et al.
2013In Nucleic Acids Research, 41 (6), p. 3699-712
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Keywords :
Animals; Cell Cycle/genetics; Cells, Cultured; E2F1 Transcription Factor/antagonists & inhibitors/metabolism; Feedback, Physiological; Gene Expression Profiling; Gene Expression Regulation; Mice; MicroRNAs/biosynthesis/metabolism; Neural Stem Cells/metabolism; Neurogenesis/genetics; RNA, Messenger/metabolism
Abstract :
[en] Stem cell fate decisions are controlled by a molecular network in which transcription factors and miRNAs are of key importance. To systemically investigate their impact on neural stem cell (NSC) maintenance and neuronal commitment, we performed a high-throughput mRNA and miRNA profiling and isolated functional interaction networks of involved mechanisms. Thereby, we identified an E2F1-miRNA feedback loop as important regulator of NSC fate decisions. Although E2F1 supports NSC proliferation and represses transcription of miRNAs from the miR-17 approximately 92 and miR-106a approximately 363 clusters, these miRNAs are transiently up-regulated at early stages of neuronal differentiation. In these early committed cells, increased miRNAs expression levels directly repress E2F1 mRNA levels and inhibit cellular proliferation. In mice, we demonstrated that these miRNAs are expressed in the neurogenic areas and that E2F1 inhibition represses NSC proliferation. The here presented data suggest a novel interaction mechanism between E2F1 and miR-17 approximately 92 / miR-106a approximately 363 miRNAs in controlling NSC proliferation and neuronal differentiation.
Disciplines :
Genetics & genetic processes
Author, co-author :
Palm, Thomas
Hemmer, Kathrin
Winter, Julia
Fricke, Inga B.
Tarbashevich, Katsiaryna
Sadeghi Shakib, Fereshteh
Rudolph, Ina-Maria
Hillje, Anna-Lena
De Luca, Paola
Bahnassawy, Lamia A
Madel, Rabea
Viel, Thomas
De Siervi, Adriana
Jacobs, Andreas H.
Diederichs, Sven
Schwamborn, Jens Christian ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
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Title :
A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1-miRNA feedback loop.
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Journal title :
Nucleic Acids Research
Publisher :
Oxford University Press, United Kingdom
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Peer reviewed :
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since 21 June 2013


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