SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia

Abstract

The brain consists of three major cell types: neurons and two glial cell types (astrocytes and oligodendrocytes). Although they are generated from common multipotent neural stem/precursor cells (NS/PCs), embryonic NS/PCs cannot generate all of the cell types at the beginning of brain development. NS/PCs first undergo extensive self‐renewal to expand their pools, and then acquire the potential to produce neurons, followed by glial cells. Astrocytes are the most frequently found cell type in the central nervous system (CNS), and play important roles in brain development and functions. Although it has been shown that nuclear factor IA (Nfia) is a pivotal transcription factor for conferring gliogenic potential on neurogenic NS/PCs by sequestering DNA methyltransferase 1 (Dnmt1) from astrocyte‐specific genes, direct targets of Nfia that participate in astrocytic differentiation have yet to be completely identified. Here we show that SRY‐box transcription factor 8 (Sox8) is a direct target gene of Nfia at the initiation of the gliogenic phase. We found that expression of Sox8 augmented leukemia inhibitory factor (LIF)‐induced astrocytic differentiation, while Sox8 knockdown inhibited Nfia‐enhanced astrocytic differentiation of NS/PCs. In contrast to Nfia, Sox8 did not induce DNA demethylation of an astrocyte‐specific marker gene, glial fibrillary acidic protein (Gfap), but instead associated with LIF downstream transcription factor STAT3 through transcriptional coactivator p300, explaining how Sox8 expression further facilitated LIF‐induced Gfap expression. Taken together, these results suggest that Sox8 is a crucial Nfia downstream transcription factor for the astrocytic differentiation of NS/PCs in the developing brain.

Sex Reversal Induced by Dietary Supplementation with 17α-Methyltestosterone during the Critical Period of Sex Differentiation in Oriental River Prawn (Macrobrachium nipponense)

“…SoxE subgroup transcription factors are thought to play essential roles in mammalian sex determination and gonadal development [ 61 , 62 ]. In teleost fish, they may only play a role in germline maintenance rather than in sexual determination [ 63 ].…”

i-Modern: Integrated multi-omics network model identifies potential therapeutic targets in glioma by deep learning with interpretability

“…To note, a significant portion of these top-ranked top signatures we identified were already found to be involved in glioma signaling in various biological pathways or mechanisms. For example, of top 20 gene expression signatures, more than half have been reported to be involved in gliomas, including BCAN, DLL3, SOX8, SPRY4, MARCKS, EDC3, MCUB, OLIG1, DKK3, ATP1A1, TUBA1B, PPFIBP1, TPM3, and MAPT [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] . For a comprehensive ranking of landmark omics signatures in patient classification, please refer to Supplemental Table S6 .…”

Profiling and Cellular Analyses of Obesity-Related circRNAs in Neurons and Glia under Obesity-like In Vitro Conditions

“…We established obesity-like condition models using brain cell lines to mimic the environment of the brains of obese individuals. These models were based on reports on the characteristics of blood serum profiling in high-fat-fed mice, rats, monkeys, and humans with obesity models [ 48 , 49 , 50 , 51 , 52 , 53 ]. Blood serum factors in obesity are important mediators in the onset of neurodegenerative diseases since the blood-brain barrier (BBB) is disrupted or loosened in obesity conditions, and consequently, blood serum factors can be delivered into brain tissue resulting in memory loss [ 54 , 55 , 56 ].…”