Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.
Tjasa LepkoMelanie PuschTamara MüllerDorothea SchulteJanina EhsesMichael A KieblerJulia HaslerHagen B HuttnerRoosmarijn E. VandenbrouckeCharysse VandendriesscheMiha ModicAna Martin-VillalbaSheng ZhaoEnric LLorens-BobadillaAnja SchneiderAndre FischerChristopher T BreunigStefan H StrickerMagdalena GötzJovica NinkovicPublished in: The EMBO journal (2019)
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.
Keyphrases
- stem cells
- cell proliferation
- long non coding rna
- cell cycle
- neural stem cells
- long noncoding rna
- cerebrospinal fluid
- spinal cord injury
- ultrasound guided
- mitral valve
- cerebral ischemia
- white matter
- heart failure
- multiple sclerosis
- cell therapy
- pulmonary artery
- blood brain barrier
- pulmonary hypertension
- coronary artery
- pulmonary arterial hypertension
- mesenchymal stem cells
- left ventricular
- human health