TY - JOUR

T1 - The role of LMNA mutations in myogenic differentiation of C2C12 and primary satellite cells

AU - Perepelina, K. I.

AU - Smolina, N. A.

AU - Zabirnik, A. S.

AU - Dmitrieva, R. I.

AU - Malashicheva, A. B.

AU - Kostareva, A. A.

N1 - Perepelina, K.I., Smolina, N.A., Zabirnik, A.S. et al. The role of LMNA mutations in myogenic differentiation of C2C12 and primary satellite cells. Cell Tiss. Biol. 11, 213–219 (2017). https://doi.org/10.1134/S1990519X17030087

PY - 2017

Y1 - 2017

N2 - Nuclear lamins form nuclear lamina located under the inner nuclear membrane. It was believed that the nuclear lamina plays predominantly a structural role. Recently, its involvement in regulatory processes have been described, e.g., chromatin organization and gene transcription. It is known that mutations in the LMNA gene lead to development of laminopathies, primarily affecting tissues of mesenchymal origin. Today, the mechanisms of the lamina regulation of cell differentiation are largely unknown. In the present work, we studied the effect of LMNA gene mutations on the process of muscle differentiation of primary satellite cells and in С2С12 cell line. The genome of satellite and С2С12 cells was modified by cell transduction via lentiviral constructs encoding LMNA G232E associated with the development of Emery–Dreyfus muscular dystrophy and LMNA R571S associated with the development of dilated cardiomyopathy. Cell morphology was assessed with immunofluorescence, and expression of myogenic genes was analyzed by qPCR. We showed that the analyzed mutations reduced the cell ability to differentiate (to fuse and to form myotubes). We proposed that these mutations enhanced expression of early and reduced expression of late markers of myogenesis. Thus, mutations in nuclear lamins can modify the process of muscle differentiation.

AB - Nuclear lamins form nuclear lamina located under the inner nuclear membrane. It was believed that the nuclear lamina plays predominantly a structural role. Recently, its involvement in regulatory processes have been described, e.g., chromatin organization and gene transcription. It is known that mutations in the LMNA gene lead to development of laminopathies, primarily affecting tissues of mesenchymal origin. Today, the mechanisms of the lamina regulation of cell differentiation are largely unknown. In the present work, we studied the effect of LMNA gene mutations on the process of muscle differentiation of primary satellite cells and in С2С12 cell line. The genome of satellite and С2С12 cells was modified by cell transduction via lentiviral constructs encoding LMNA G232E associated with the development of Emery–Dreyfus muscular dystrophy and LMNA R571S associated with the development of dilated cardiomyopathy. Cell morphology was assessed with immunofluorescence, and expression of myogenic genes was analyzed by qPCR. We showed that the analyzed mutations reduced the cell ability to differentiate (to fuse and to form myotubes). We proposed that these mutations enhanced expression of early and reduced expression of late markers of myogenesis. Thus, mutations in nuclear lamins can modify the process of muscle differentiation.

KW - laminopathies

KW - muscle differentiation

KW - nuclear lamins

KW - primary satellite cells

KW - С2С12 cell line

UR - http://www.scopus.com/inward/record.url?scp=85020471567&partnerID=8YFLogxK

U2 - 10.1134/S1990519X17030087

DO - 10.1134/S1990519X17030087

M3 - Article

AN - SCOPUS:85020471567

VL - 11

SP - 213

EP - 219

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 3

ER -