RE1 silencing transcription factor/neuron‐restrictive silencing factor regulates expansion of adult mouse subventricular zone‐derived neural stem/progenitor cells in vitro

Abstract

Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST‐mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome‐ and transcriptome‐wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST‐regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. © 2015 Wiley Periodicals, Inc.

Differential Transcription Profiling in Bone Marrow Mononuclear Cells Between Myasthenia Gravis Patients With or Without Thymoma

“…REST is a zinc nger transcription factor that plays negatively regulated roles in neuronal stem and progenitor cell (NSPC) development and differentiation by recruiting transcriptional and epigenetic regulatory cofactors to repressor element-1 in the promoter regions of neuronal genes [34,35] . Recent studies [36] showed that in the T cell/neuron coculture model, activated CD4 + T cells reduced the activity of neurons and extracellular signal-regulated kinase 1/2, causing REST mRNA upregulation and thereby mediating the downregulation of REST-mediated neuronal cell adhesion molecule L1, which exhibited an unexpected functions in the pathological crosstalk between the immune and nervous systems.…”

Egr-1 Maintains NSC Proliferation and Its Overexpression Counteracts Cell Cycle Exit Triggered by the Withdrawal of Epidermal Growth Factor

“…Cultured under adherent conditions in EGF + bFGF expansion medium, these cells express several stem cell markers including Sox2 and nestin [27]. Under these conditions, about 70% of cells were positive for Ki67, a marker of proliferation.…”