A MiR-124-mediated Post-transcriptional Mechanism Controlling the Cell Fate Switch of Astrocytes to Induced Neurons

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2023 Mar 24

PMID 36963393

Authors

Elsa Papadimitriou

Paraskevi N Koutsoudaki

Irini Thanou

Dimitra Karagkouni

Timokratis Karamitros

Dafni Chroni-Tzartou

Maria Gaitanou

Christos Gkemisis

Maria Margariti

Evangelia Xingi

Socrates J Tzartos

Artemis G Hatzigeorgiou

Dimitra Thomaidou

Affiliations

Soon will be listed here.

Abstract

The microRNA (miRNA) miR-124 has been employed supplementary to neurogenic transcription factors (TFs) and other miRNAs to enhance direct neurogenic conversion. The aim of this study was to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced neurons (iNs) on its own and elucidate its independent mechanism of reprogramming action. Our data show that miR-124 is a potent driver of the reprogramming switch of astrocytes toward an immature neuronal fate by directly targeting the RNA-binding protein Zfp36L1 implicated in ARE-mediated mRNA decay and subsequently derepressing Zfp36L1 neurogenic interactome. To this end, miR-124 contribution in iNs' production largely recapitulates endogenous neurogenesis pathways, being further enhanced upon addition of the neurogenic compound ISX9, which greatly improves iNs' differentiation and functional maturation. Importantly, miR-124 is potent in guiding direct conversion of reactive astrocytes to immature iNs in vivo following cortical trauma, while ISX9 supplementation confers a survival advantage to newly produced iNs.

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