Abstract
A-type lamins are the main structural components of the nucleus, which are mainly localized at the nucleus periphery. First of all, A-type lamins, together with B-type lamins and proteins of the inner nuclear membrane, form a stiff structure—the nuclear lamina. Besides maintaining the nucleus cell shape, A-type lamins play a critical role in many cellular events, such as gene transcription and epigenetic regulation. Nowadays it is clear that lamins play a very important role in determining cell fate decisions. Various mutations in genes encoding A-type lamins lead to damages of different types of tissues in humans, collectively known as laminopathies, and it is clear that A-type lamins are involved in the regulation of cell differentiation and stemness. However, the mechanisms of this regulation remain unclear. In this review, we discuss how A-type lamins can execute their regulatory role in determining the differentiation status of a cell. We have summarized recent data focused on lamin A/C action mechanisms in regulation of cell differentiation and identity development of stem cells of different origin. We also discuss how this knowledge can promote further research toward a deeper understanding of the role of lamin A/C mutations in laminopathies.
Highlights
A-type lamins are the structural components of the nucleus, which together with B-type lamins and inner nuclear membrane proteins form a scaffold, termed the nuclear lamina
Laminopathies are a group of hereditary diseases caused by mutations in genes encoding (a) nuclear lamins; (b) proteins associated with post-translational modifications of lamins; (c) proteins that interact with lamins, and (d) proteins that make up nuclear pores (Zaremba-Czogalla et al, 2011)
Nuclear A-type lamins play a critical role in vital cell functions including migration, growth, homeostasis, proliferation, differentiation, and many others
Summary
A-type lamins are the structural components of the nucleus, which together with B-type lamins and inner nuclear membrane proteins form a scaffold, termed the nuclear lamina. During cell differentiation A-type lamins get information about the changing microenvironment from nearby cells and ECM through the cytoskeleton This leads to a rearranging meshwork and chromatin structures, or urges conformational changes in nuclear proteins such as transcription factors and components of signaling pathways. Lamin A/C overexpression leads to an inhibition of chromatin remodeling, and to an activation of other actions such as expression of stress-related proteins implicated in cell differentiation, and transcriptional regulator YAP1 involved in cell proliferation and the suppression of apoptotic genes and Hippo pathway (Swift et al, 2013). Mechanical signals coming from the intercellular matrix can direct lamins to proper stabilization of the genome in response to mechanical stress and tissue-specific gene expression during cell differentiation These events are necessary to support nucleus shape and prevent the DNA from breaking. The implication of Wnt/β-catenin signaling in osteogenic differentiation promotion of MSCs was confirmed in several studies (Tong et al, 2011; Wang et al, 2017), whereas adipogenic and chondrogenic direction of differentiation was suppressed when Wnt/β-catenin was activated (Case and Rubin, 2010; Ullah et al, 2015)
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