Role of the Proteins of the Nuclear Envelope in Mesenchymal Stem Cell Differentiation

Abstract

The nuclear envelope (NE) provides stiffness to the nucleus, protects the genome, and regulates the mechanotransduction process via its network of proteins. These roles govern gene transcription and cell survival and/or differentiation. Considering that these proteins transmit cytoplasmic signalling to the nucleus through interactions with transcription factors, the identification and control of these interactions could play an important role in the regulation of cell differentiation and survival. In mesenchymal stem cells (MSCs), it has been demonstrated that NE proteins are crucial to the differentiation process. Mutations in some of them are linked to envelopathies, in which mesenchymal tissues are differentially affected. In addition, during the ageing process, their level is decreased, which would explain in part some of the age-related changes in bone and muscle. Lamin A, emerin and MAN1 are the most studied NE proteins in terms of their involvement in the pathogenesis of envelopathies. In this thesis we hypothesized that these NE proteins are involved in the differentiation of MSCs into bone and fat, playing a role in the pathogenesis of age-related bone loss. Therefore, this research thesis reports new evidence on the role of these three proteins during osteoblastic and adipogenic differentiation of bone marrow-derived human MSCs.