The transcription factor MEF2A plays a key role in the differentiation/maturation of rat neural stem cells into neurons

Zhu, Bangfu; Carmichael, Ruth E.; Valois, Luis Solabre; Wilkinson, Kevin A.; Henley, Jeremy M.

doi:10.1016/j.bbrc.2018.04.125

Cited by 21 publications

(22 citation statements)

References 21 publications

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“…We then focused on the TFs expressed in each of the maSigPro clusters, as they may play a role in the regulation of differentiation into each cell type. As expected, TFs that showed increased expression in NPC clusters include those important in neuronal development and overall expression of early neurons such as Pax6 (RR11), Jun (RR5), Mef2a (RR8), Mef2c (RR11), Tead2 (RR1), Sox9 (RR1), and bhlhe40 (RR8) (Zhu et al 2018); (Cho et al 2011;Dietrich 2013); ("YAP/TAZ Enhance Mammalian Embryonic Neural Stem Cell Characteristics in a Tead-Dependent Manner" 2015)). Similarly, the TFs in clusters that increase during DE differentiation include important markers of DE development and differentiation such as…”

Section: Distinct Transcriptional and Chromatin Accessibility Trajectmentioning

confidence: 64%

Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat

Jiang²,

Roxas³

et al. 2021

Preprint

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Differentiation of cell types homologous between species are controlled by conserved networks of regulatory elements driving gene expression. In order to identify conservation of gene expression and chromatin accessibility during cell differentiation in two different species. We collected a daily time-course of gene expression and chromatin accessibility in rat and human to quantify conserved and species-specific chromatin dynamics during embryonic stem cell differentiation to definitive endoderm (DE) as well as to neuronal progenitor cells (NPC). We identify shared and cell-type specific transient differentiation markers in each species, including key transcription factors that may regulate differentiation into each cell-type and their candidate cis-regulatory elements (cCREs). Our analysis shows that DE differentiation has higher conservation of gene expression and chromatin accessibility than NPC differentiation. We provide the first global comparison of transcriptional complexity and chromatin dynamics between human and rat for DE and NPC differentiation.

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Section: Distinct Transcriptional and Chromatin Accessibility Trajectmentioning

confidence: 64%

Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat

Jiang²,

Roxas³

et al. 2021

Preprint

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“…Chd1 depletion robustly enhanced TDP-43-mediated neurodegeneration and promoted the formation of stress granules [ 99 ]. Mef2a was shown to play a key role in the differentiation and maturation of rat neural stem cells into neurons [ 100 ]. Reducing Mef2a activity was shown to be involved in Parkinson's disease features in model animals [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

Wei

et al. 2021

BioMed Research International

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Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resulting from stress and neurological impairment in different brain regions are still unclear. To clarify the pathological changes in the dentate gyrus (DG) and anterior cingulate cortex (ACC) regions of the MDD brain, which are the most closely related to the disease, we investigated the published microarray profile dataset GSE84183 to identify unpredictable chronic mild stress- (UCMS-) induced differentially expressed genes (DEGs) in the DG and ACC regions. Based on the DEG data, functional annotation, protein-protein interaction, and transcription factor (TF) analyses were performed. In this study, 1071 DEGs (679 upregulated and 392 downregulated) and 410 DEGs (222 upregulated and 188 downregulated) were identified in DG and ACC, respectively. The pathways and GO terms enriched by the DEGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate immune responses, cell migration, and circadian rhythm. Sixteen hub genes in the DG (Fn1, Col1a1, Anxa1, Penk, Ptgs2, Cdh1, Timp1, Vim, Rpl30, Rps21, Dntt, Ptk2b, Jun, Avp, Slit1, and Sema5a) were identified. Eight hub genes in the ACC (Prkcg, Grin1, Syngap1, Rrp9, Grwd1, Pik3r1, Hnrnpc, and Prpf40a) were identified. In addition, eleven TFs (Chd2, Zmiz1, Myb, Etv4, Rela, Tcf4, Tcf12, Chd1, Mef2a, Ubtf, and Mxi1) were predicted to regulate more than two of these hub genes. The expression levels of ten randomly selected hub genes that were specifically differentially expressed in the MDD-like animal model were verified in the corresponding regions in the human brain. These hub genes and TFs may be regarded as potential targets for future MDD treatment strategies, thus aiding in the development of new therapeutic approaches to MDD.

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“…Studies indicate that MEF-2A is present in undifferentiated neural stem cells, and after subsequent differentiation exhibit higher amounts in neuronal cells. MEF-2A plays a critical role in differentiation and maturation of neural stem cells into neurons in rat models [165]. MEF-2 transcriptional activity is also activated by neurotrophins such as brain-derived neurotrophic factor (BDNF) via Nur77 and ARC through a novel pathway in rat cortical neurons [166].…”

Section: Regulation Of Mef-2mentioning

confidence: 99%

MEF-2 isoforms' (A-D) roles in development and tumorigenesis

et al. 2019

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Myocyte enhancer factor (MEF)-2 plays a critical role in proliferation, differentiation, and development of various cell types in a tissue specific manner. Four isoforms of MEF-2 (A-D) differentially participate in controlling the cell fate during the developmental phases of cardiac, muscle, vascular, immune and skeletal systems. Through their associations with various cellular factors MEF-2 isoforms can trigger alterations in complex protein networks and modulate various stages of cellular differentiation, proliferation, survival and apoptosis. The role of the MEF-2 family of transcription factors in the development has been investigated in various cell types, and the evolving alterations in this family of transcription factors have resulted in a diverse and wide spectrum of disease phenotypes, ranging from cancer to infection. This review provides a comprehensive account on MEF-2 isoforms (A-D) from their respective localization, signaling, role in development and tumorigenesis as well as their association with histone deacetylases (HDACs), which can be exploited for therapeutic intervention.

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The transcription factor MEF2A plays a key role in the differentiation/maturation of rat neural stem cells into neurons

Cited by 21 publications

References 21 publications

Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat

Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

MEF-2 isoforms' (A-D) roles in development and tumorigenesis

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