Mediator Med23 Regulates Adult Hippocampal Neurogenesis

Abstract

Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-Cre ER :Med23 flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP + /Sox2 + NSCs and Tbr2 + progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.

Recent advances in nucleotide analogue-based techniques for tracking dividing stem cells: An overview

“…Another group of animals receive two labels separated by a time interval longer than the difference between the cell cycle length and the S-phase duration, and subsequent cell quantifications enable the calculation of the cell cycle length. This approach can be applied when we need to test whether any physiological or pathological stimulus alters the cell cycle parameters of a given population of proliferating cells ( 113 , 114 , 115 , 116 ).…”

Mediator complex proximal Tail subunit MED30 is critical for Mediator core stability and cardiomyocyte transcriptional network

“…It is of relevance to note that deletion of individual MED subunits in B cell, T cell, and embryonic stem cells (ESC) revealed that only a fraction of genes was affected and that the number of differentially expressed genes was variable in different cell types, although the overall viability of cells was dramatically decreased [35]. Variation in the number of genes affected by MED subunit deletion has also been widely recognized in multiple other cell types, such as deletion of MED23 in mouse embryonic stem cells (ESCs) [47], mouse embryonic fibroblasts (MEFs) [48], mesenchymal stem cells [49], hematopoietic stem cells [50], adult hippocampal neural stem cells (NSCs) [51] and hepatocytes [52]. Another possible explanation for the large difference in the number of genes differentially expressed consequent to MED30 ablation in embryonic versus adult heart, is that, in embryonic heart, RNAseq was performed at E10.5, prior to onset of overt cardiac phenotypes, therefore likely excluding secondary gene changes.…”

Oar-miR-432 Regulates Fat Differentiation and Promotes the Expression of BMP2 in Ovine Preadipocytes

“…The data were uploaded in the SRA database ( https://www.ncbi.nlm.nih.gov/sra ) as PRJNA792697 and PRJNA777369. The significant enrichment of Gene Ontology (GO) functional terms with overlapped genes that showed differential expression was analyzed, which covered the three domains of cellular component, molecular function, and biological process ( Chen et al, 2020 ).…”