Piwil2 (Mili) sustains neurogenesis and prevents cellular senescence in the postnatal hippocampus

Abstract: Adult neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate has thus important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) have been proposed to control memory and anxiety, but the mechanism remains elusive. Here, we show that Piwil2 (Mili) is essential for proper neurogenesis in the postnatal mouse hippocampus. RNA sequencing of aNPCs and their differentiated progeny reveal that Mili and piRNAs are dynamically expressed in neurogenesis. Depletion of Mili and piRNAs in the adult hippocampus impairs aNPC differentiation toward a neural fate, induces senescence, and generates reactive glia. Transcripts modulated upon Mili depletion bear sequences complementary or homologous to piRNAs and include repetitive elements and mRNAs encoding essential proteins for proper neurogenesis. Our results provide evidence of a critical role for Mili in maintaining fitness and proper fate of aNPCs, underpinning a possible involvement of the piRNA pathway in brain plasticity and successful aging.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Piwil2 (Mili) sustains neurogenesis and prevents cellular senescence in the postnatal hippocampus ; day:06 ; month:12 ; year:2022 ; extent:28
EMBO reports / European Molecular Biology Organization ; (06.12.2022) (gesamt 28)

Urheber
Gasperini, Caterina
Tuntevski, Kiril
Beatini, Silvia
Pelizzoli, Roberta
Lo Van, Amanda
Mangoni, Damiano
Cossu, Rosa M.
Pascarella, Giovanni
Bianchini, Paolo
Bielefeld, Pascal
Scarpato, Margherita
Pons‐Espinal, Meritxell
Sanges, Remo
Diaspro, Alberto
Fitzsimons, Carlos P.
Carninci, Piero
Gustincich, Stefano
De Pietri Tonelli, Davide

DOI
10.15252/embr.202153801
URN
urn:nbn:de:101:1-2022120614345764267195
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:34 MESZ

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Beteiligte

  • Gasperini, Caterina
  • Tuntevski, Kiril
  • Beatini, Silvia
  • Pelizzoli, Roberta
  • Lo Van, Amanda
  • Mangoni, Damiano
  • Cossu, Rosa M.
  • Pascarella, Giovanni
  • Bianchini, Paolo
  • Bielefeld, Pascal
  • Scarpato, Margherita
  • Pons‐Espinal, Meritxell
  • Sanges, Remo
  • Diaspro, Alberto
  • Fitzsimons, Carlos P.
  • Carninci, Piero
  • Gustincich, Stefano
  • De Pietri Tonelli, Davide

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