Document Type

Article

Publication Date

7-12-2021

Publication Title

Cells

Keywords

JGM, Animals, Base Sequence, Cell Differentiation, Down-Regulation, Gene Deletion, Gene Expression Regulation, Genome, Lentivirus, Mice, Models, Biological, Neural Stem Cells, Neuroglia, Neurons, Proto-Oncogene Proteins c-fos, RNA-Seq, SOXB1 Transcription Factors, Suppressor of Cytokine Signaling 3 Protein, Transcription Factor AP-1

JAX Source

Cells 2021 Jul 12; 10(7):1757

Volume

10

Issue

7

ISSN

2073-4409

PMID

34359927

DOI

https://doi.org/10.3390/cells10071757

Abstract

The transcription factor SOX2 is important for brain development and for neural stem cells (NSC) maintenance. Sox2-deleted (Sox2-del) NSC from neonatal mouse brain are lost after few passages in culture. Two highly expressed genes, Fos and Socs3, are strongly downregulated in Sox2-del NSC; we previously showed that Fos or Socs3 overexpression by lentiviral transduction fully rescues NSC's long-term maintenance in culture. Sox2-del NSC are severely defective in neuronal production when induced to differentiate. NSC rescued by Sox2 reintroduction correctly differentiate into neurons. Similarly, Fos transduction rescues normal or even increased numbers of immature neurons expressing beta-tubulinIII, but not more differentiated markers (MAP2). Additionally, many cells with both beta-tubulinIII and GFAP expression appear, indicating that FOS stimulates the initial differentiation of a "mixed" neuronal/glial progenitor. The unexpected rescue by FOS suggested that FOS, a SOX2 transcriptional target, might act on neuronal genes, together with SOX2. CUT&RUN analysis to detect genome-wide binding of SOX2, FOS, and JUN (the AP1 complex) revealed that a high proportion of genes expressed in NSC are bound by both SOX2 and AP1. Downregulated genes in Sox2-del NSC are highly enriched in genes that are also expressed in neurons, and a high proportion of the "neuronal" genes are bound by both SOX2 and AP1.

Comments

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

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