Investigating the role of nuclear lamins in regulating the stemness and neuronal differentiation of NT2/D1 embryonal carcinoma cells

Abstract

Cells undergo transition in lineages from one cell type to another with major alterations in their transcriptomic signatures. This is facilitated by changes in their nuclear and genomic architecture, largely brought about by the responses of key nuclear envelope proteins, including lamins and nucleoporins. Lamins are type-V intermediate filament proteins that provide structural integrity to the nucleus and also regulate chromatin architecture and gene expression. Differentiation of the pluripotent NT2/D1 cells into specialised neuronal cells serves as a useful model to study the mechanistic roles of the different lamin subtypes in regulating the highly dynamic processes involved in cell fate transition. In this study, the three lamin subtypes- A, B1 and B2, in association with proteins of the nucleoporin-93 (NUP93) subcomplex, have been shown to play a significant role in distinctly modulating the stemness of the pluripotent NT2/D1 cells, as well as differentially regulating the initiation and progression of differentiation of these cells along the neuronal lineage in a temporally regulated manner. We speculate that the lamins facilitate neuronal differentiation by directly impacting the gene expression of specific pluripotency and differentiation factors.