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Lepko, Tjasa; Pusch, Melanie; Müller, Tamara; Schulte, Dorothea; Ehses, Janina; Kiebler, Michael; Hasler, Julia; Huttner, Hagen B.; Vandenbroucke, Roosmarijn E.; Vandendriessche, Charysse; Modic, Miha; Martin-Villalba, Ana; Zhao, Sheng; LLorens-Bobadilla, Enric; Schneider, Anja; Fischer, Andre; Breunig, Christopher T.; Stricker, Stefan H.; Götz, Magdalena; Ninkovic, Jovica (2019): Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain. In: EMBO Journal, Vol. 38, No. 17, e100481
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Abstract

Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells.