Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling

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Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling. / Perepelina, K.; Dmitrieva, R.; Ignatieva, E.; Borodkina, A.; Kostareva, A.; Malashicheva, A.

In: Biochemistry and Cell Biology, Vol. 96, No. 3, 06.2018, p. 342-348.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{02eeb5b426344ed6a5ae29aa2b3ad4e5,

title = "Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling",

abstract = "Lamins A and C are involved in many cellular functions, owing to its ability to bind chromatin and transcription factors and affect their properties. Mutations of the LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, the signaling pathways involved in interactions with lamins during cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in the adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated through the expression of Notch-responsive genes by qPCR and by activation of a luciferase CSL-reporter construct. The effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that, when Notch is activated, LMNA R482L contributes to down-regulation of Notch activation in undifferentiated and differentiated cells, and decreases adipogenic differentiation. Thus, lamin A/C interacts with Notch signaling, thereby influencing cellular differentiation, and point mutation in LMNA could halt this interaction.",

keywords = "Adipogenic differentiation, Dunnigan-type familial partial lipodystrophy, Lamin A/C, Notch signaling, Chromatin/metabolism, Mutation/genetics, Humans, Signal Transduction/genetics, Rats, Receptors, Notch/metabolism, Mesenchymal Stem Cells/metabolism, Lamin Type A/genetics, Lipodystrophy/genetics, Stem Cells/metabolism, Animals, Cell Differentiation/genetics, Adipogenesis/genetics, DOMAIN, NUCLEAR-MEMBRANE, lamin A/C, PROGENITOR CELLS, A-TYPE LAMINS, EMERIN, FAMILIAL PARTIAL LIPODYSTROPHY, adipogenic differentiation, TRANSCRIPTION, CATENIN, FAILURE, DYNAMICS",

author = "K. Perepelina and R. Dmitrieva and E. Ignatieva and A. Borodkina and A. Kostareva and A. Malashicheva",

year = "2018",

month = jun,

doi = "10.1139/bcb-2017-0210",

language = "English",

volume = "96",

pages = "342--348",

journal = "Biochemistry and Cell Biology",

issn = "0829-8211",

publisher = "National Research Council of Canada",

number = "3",

}

RIS

TY - JOUR

T1 - Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling

AU - Perepelina, K.

AU - Dmitrieva, R.

AU - Ignatieva, E.

AU - Borodkina, A.

AU - Kostareva, A.

AU - Malashicheva, A.

PY - 2018/6

Y1 - 2018/6

N2 - Lamins A and C are involved in many cellular functions, owing to its ability to bind chromatin and transcription factors and affect their properties. Mutations of the LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, the signaling pathways involved in interactions with lamins during cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in the adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated through the expression of Notch-responsive genes by qPCR and by activation of a luciferase CSL-reporter construct. The effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that, when Notch is activated, LMNA R482L contributes to down-regulation of Notch activation in undifferentiated and differentiated cells, and decreases adipogenic differentiation. Thus, lamin A/C interacts with Notch signaling, thereby influencing cellular differentiation, and point mutation in LMNA could halt this interaction.

AB - Lamins A and C are involved in many cellular functions, owing to its ability to bind chromatin and transcription factors and affect their properties. Mutations of the LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, the signaling pathways involved in interactions with lamins during cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in the adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated through the expression of Notch-responsive genes by qPCR and by activation of a luciferase CSL-reporter construct. The effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that, when Notch is activated, LMNA R482L contributes to down-regulation of Notch activation in undifferentiated and differentiated cells, and decreases adipogenic differentiation. Thus, lamin A/C interacts with Notch signaling, thereby influencing cellular differentiation, and point mutation in LMNA could halt this interaction.

KW - Adipogenic differentiation

KW - Dunnigan-type familial partial lipodystrophy

KW - Lamin A/C

KW - Notch signaling

KW - Chromatin/metabolism

KW - Mutation/genetics

KW - Humans

KW - Signal Transduction/genetics

KW - Rats

KW - Receptors, Notch/metabolism

KW - Mesenchymal Stem Cells/metabolism

KW - Lamin Type A/genetics

KW - Lipodystrophy/genetics

KW - Stem Cells/metabolism

KW - Animals

KW - Cell Differentiation/genetics

KW - Adipogenesis/genetics

KW - DOMAIN

KW - NUCLEAR-MEMBRANE

KW - lamin A/C

KW - PROGENITOR CELLS

KW - A-TYPE LAMINS

KW - EMERIN

KW - FAMILIAL PARTIAL LIPODYSTROPHY

KW - adipogenic differentiation

KW - TRANSCRIPTION

KW - CATENIN

KW - FAILURE

KW - DYNAMICS

UR - http://www.scopus.com/inward/record.url?scp=85047930611&partnerID=8YFLogxK

UR - http://www.nrcresearchpress.com/doi/10.1139/bcb-2017-0210

UR - http://www.mendeley.com/research/lamin-ac-mutation-associated-lipodystrophy-influences-adipogenic-differentiation-stem-cells-through

U2 - 10.1139/bcb-2017-0210

DO - 10.1139/bcb-2017-0210

M3 - Article

C2 - 29040816

AN - SCOPUS:85047930611

VL - 96

SP - 342

EP - 348

JO - Biochemistry and Cell Biology

JF - Biochemistry and Cell Biology

SN - 0829-8211

IS - 3

ER -

ID: 35805320