The role of nuclear membrane proteins in differentiation and chromatin organization

Abstract: The nuclear envelope, consisting of an outer and an inner nuclear membrane, surrounds the genomic material. The genomic material (chromatin) is highly structured with (transcriptionally inactive) heterochromatin mostly found in the nuclear periphery and (transcriptionally active) euchromatin mostly found in the nuclear interior. Underlying the nuclear envelope is the nuclear lamina that consists of lamin proteins and nuclear envelope transmembrane proteins (NETs), which organize chromatin in the nuclear periphery. There are several hundred uncharacterized tissue-specific NETs, with only a few linked to cellular differentiation. Induced pluripotent stem cells (iPSCs) enable studies of early differentiation and are a promising tool for cell replacement therapies.In this licentiate thesis, we have focused on investigating the role of the inner nuclear membrane protein Samp1 in chromatin organization and cell differentiation. Overexpression of Samp1 induced a fast differentiation of iPSCs, suggesting that Samp1 may be involved in the differentiation process. We have also developed a novel image analysis method to be able to monitor chromatin organization in live cells. Depletion of Samp1 affected chromatin distribution and resulted in increased formation of peripheral heterochromatin, contradictory to what is expected of other characterized NETs. It is possible that Samp1 might have a role in both differentiation and chromatin organization and that future studies might link these two processes together.