SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize Nfib mRNA

Abstract
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Abstract

Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here we addressed how murine adult hippocampal NSC fate is regulated and describe how Scaffold Attachment Factor B (SAFB) blocks oligodendrocyte production to enable neuron generation. We found that SAFB prevents NSC expression of the transcription factor Nuclear Factor I/B (NFIB) by binding to sequences in the Nfib mRNA and enhancing Drosha-dependent cleavage of the transcripts. We show that increasing SAFB expression prevents oligodendrocyte production by multipotent adult NSCs, and conditional deletion of Safb increases NFIB expression and oligodendrocyte formation in the adult hippocampus. Our results provide novel insights into a mechanism that controls Drosha functions for selective regulation of NSC fate by modulating the post-transcriptional destabilization of Nfib mRNA in a lineage-specific manner.

Data availability

Proteomics mass spectrometry data have been deposited in PRIDE:Project accession: PXD017677Project DOI: 10.6019/PXD017677

The following data sets were generated

1. Taylor V et al
(2024) SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize Nfib mRNA
EBI PRIDE, PXD017677.

https://www.ebi.ac.uk/pride/archive/projects/PXD017677

Article and author information

Author details

Pascal Forcella

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Niklas Ifflander

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Chiara Rolando

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Elli-Anna Balta

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Aikaterini Lampada

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Claudio Giachino

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Tanzila Mukhtar

Department of Biomedicine, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.
Thomas Bock

Proteomics Core Facility, University of Basel, Basel, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9314-5318
Verdon Taylor

Department of Biomedicine, University of Basel, Basel, Switzerland

For correspondence
verdon.taylor@unibas.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3497-5976

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_162609)

Verdon Taylor

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_182388)

Verdon Taylor

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: According to Swiss Federal and Swiss Veterinary office regulations, all mice were bred and kept in a specific pathogen-free animal facility with 12 hours day-night cycle and free access to clean food and water. All mice were healthy and immunocompetent. All procedures were approved by the Basel Cantonal Veterinary Office under license number 2537 (Ethics commission Basel-Stadt, Basel Switzerland).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.