RUNX transcription factors are essential in maintaining epididymal epithelial differentiation.
Mervi TorisevaIda BjörkgrenArttu JunnilaArfa MehmoodJesse MattssonInka RaimorantaBongki KimAsta LaihoMatthias NeesLaura EloMatti PoutanenSylvie BretonPetra SipiläPublished in: Cellular and molecular life sciences : CMLS (2024)
Apart from the androgen receptor, transcription factors (TFs) that are required for the development and formation of the different segments of the epididymis have remained unknown. We identified TF families expressed in the developing epididymides, of which many showed segment specificity. From these TFs, down-regulation of runt related transcription factors (RUNXs) 1 and 2 expression coincides with epithelial regression in Dicer1 cKO mice. Concomitant deletion of both Runx1 and Runx2 in a mouse epididymal epithelial cell line affected cell morphology, adhesion and mobility in vitro. Furthermore, lack of functional RUNXs severely disturbed the formation of 3D epididymal organoid-like structures. Transcriptomic analysis of the epididymal cell organoid-like structures indicated that RUNX1 and RUNX2 are involved in the regulation of MAPK signaling, NOTCH pathway activity, and EMT-related gene expression. This suggests that RUNXs are master regulators of several essential signaling pathways, and necessary for the maintenance of proper differentiation of the epididymal epithelium.
Keyphrases
- transcription factor
- single cell
- gene expression
- dna binding
- signaling pathway
- cell therapy
- genome wide identification
- high resolution
- poor prognosis
- epithelial mesenchymal transition
- dna methylation
- stem cells
- cell proliferation
- rna seq
- pi k akt
- mesenchymal stem cells
- cystic fibrosis
- binding protein
- mass spectrometry
- long non coding rna