title: Various lamin A/C mutations alter expression profile of mesenchymal stem cells in mutation specific manner.
abstract: Various mutations in LMNA gene, encoding for nuclear lamin A/C protein, lead to laminopathies and contribute to over ten human disorders, mostly affecting tissues of mesenchymal origin such as fat tissue, muscle tissue, and bones. Recently it was demonstrated that lamins not only play a structural role providing communication between extra-nuclear structures and components of cell nucleus but also control cell fate and differentiation. In our study we assessed the effect of various LMNA mutations on the expression profile of mesenchymal multipotent stem cells (MMSC) during adipogenic and osteogenic differentiation. We used lentiviral approach to modify human MMSC with LMNA-constructs bearing mutations associated with different laminopathies--G465D, R482L, G232E, R527C, and R471C. The impact of various mutations on MMSC differentiation properties and expression profile was assessed by colony-forming unit analysis, histological staining, expression of the key differentiation markers promoting adipogenesis and osteogenesis followed by the analysis of the whole set of genes involved in lineage-specific differentiation using PCR expression arrays. We demonstrate that various LMNA mutations influence the differentiation efficacy of MMSC in mutation-specific manner. Each LMNA mutation promotes a unique expression pattern of genes involved in a lineage-specific differentiation and this pattern is shared by the phenotype-specific mutations.
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia; St. Petersburg State University, St. Petersburg, Russia; ITMO University, Institute of translational Medicine, St. Petersburg, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Malashicheva
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia; St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Bogdanova
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Arsenii
authors.initials: A
authors.lastname: Zabirnyk
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia; Department of Woman and Child Health, Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Smolina
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Ignatieva
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Freilikhman
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Fedorov
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Renata
authors.initials: R
authors.lastname: Dmitrieva
authors.affiliation: Department of Woman and Child Health, Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sjöberg
authors.affiliation: Department of Woman and Child Health, Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sejersen
authors.affiliation: Almazov Federal Medical Research Centre, St. Petersburg, Russia; Department of Woman and Child Health, Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; ITMO University, Institute of translational Medicine, St. Petersburg, Russia. Electronic address: anna.kostareva@ki.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Kostareva
mesh_terms: D050156:Adipogenesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D034882:Lamins / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009154:Mutation; D010012:Osteogenesis; D059467:Transcriptome
chemical_list: D034882:Lamins; C000605834:lamin C protein, human; D006655:Histone Deacetylases
keywords: Differentiation; Expression profile; Lamin A/C; Multipotent mesenchymal stem cells; Mutation