Unknown,Transcriptomics,Genomics,Proteomics

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CUT&RUN Targeting c-FOS, c-JUN and SOX2 in neurospheres derived from mouse brain cells


ABSTRACT: Other than in the development of the brain, SOX2 is essential for the long-term self-renewal of neural stem cells (NSCs). The mechanisms of how SOX2 maintains the stemness of NSCs is not yet understood. We have identified Fos as a downstream target of SOX2, and therefore used CUT&RUN to investigate where these transcription factors - and the c-FOS partner c-JUN - interact with the genome. By comparing binding patterns of c-FOS, c-JUN and SOX2, we find that they co-occupate the promoter of the SOCS3 locus, which we also have identified as a gene that rescues SOX2 deletion induced senescence when overexpressed in neurospheres grown from Sox2-deleted mouse NSCs. Taken together, our data provide a basis for elucidating a gene regulatory network necessary for the maintenance of self-renewal in post-embryonic neural stem cells.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Mus musculus

SUBMITTER: Mattias Pernebrink 

PROVIDER: E-MTAB-9897 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network.

Pagin Miriam M   Pernebrink Mattias M   Giubbolini Simone S   Barone Cristiana C   Sambruni Gaia G   Zhu Yanfen Y   Chiara Matteo M   Ottolenghi Sergio S   Pavesi Giulio G   Wei Chia-Lin CL   Cantù Claudio C   Nicolis Silvia K SK  

Stem cells (Dayton, Ohio) 20210329 8


The Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSCs). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2), individually or in combination. Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Furthermore, pha  ...[more]

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