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Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.

EMBO J. 2019 Jul 15:e100481. doi: 10.15252/embj.2018100481. [Epub ahead of print]

Authors/Editors: Lepko T, Pusch M, Müller T, Schulte D, Ehses J, Kiebler M, Hasler J, Huttner HB, Vandenbroucke RE, Vandendriessche C, Modic M, Martin-Villalba A, Zhao S, LLorens-Bobadilla E, Schneider A, Fischer A, Breunig CT, Stricker SH, Götz M, Ninkovic J.
Publication Date: 2019

07_lepko

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.

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