title: A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1-miRNA feedback loop.
abstract: 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∼92 and miR-106a∼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∼92 / miR-106a∼363 miRNAs in controlling NSC proliferation and neuronal differentiation.
authors: Westfälische Wilhelms-Universität Münster, ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, 48149 Münster, Germany.
authors: Thomas
authors: T
authors: Palm
authors: Kathrin
authors: K
authors: Hemmer
authors: Julia
authors: J
authors: Winter
authors: Inga B
authors: IB
authors: Fricke
authors: Katsiaryna
authors: K
authors: Tarbashevich
authors: Fereshteh
authors: F
authors: Sadeghi Shakib
authors: Ina-Maria
authors: IM
authors: Rudolph
authors: Anna-Lena
authors: AL
authors: Hillje
authors: Paola
authors: P
authors: De Luca
authors: Lamia'a
authors: L
authors: Bahnassawy
authors: Rabea
authors: R
authors: Madel
authors: Thomas
authors: T
authors: Viel
authors: Adriana
authors: A
authors: De Siervi
authors: Andreas H
authors: AH
authors: Jacobs
authors: Sven
authors: S
authors: Diederichs
authors: Jens C
authors: JC
authors: Schwamborn
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger
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