Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis.
Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis.
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DOI：
10.3390/ijms22126580
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发表时间：
2021-06-19
影响因子：
5.6
通讯作者：
Uzer G
中科院分区：
文献类型：
--
作者：
Goelzer M;Dudakovic A;Olcum M;Sen B;Ozcivici E;Rubin J;van Wijnen AJ;Uzer G
间充质干细胞（MSCs）通过分化成多个细胞系（包括成骨细胞和脂肪细胞）来维持肌肉骨骼系统。机械信号，包括应变和低强度振动（LIV），是通过细胞结构施加控制的间充质干细胞分化的重要调节因子。核纤层蛋白A/C是一种对细胞核结构至关重要的蛋白质，它支持染色质组织和分化，并有助于细胞核的机械完整性。我们研究了层粘连蛋白A/C和机械反应性是否在MSCs的脂肪形成过程中功能耦合。膜层蛋白A/C的siRNA损耗增加了核的面积、高度和体积，降低了核的圆度和刚度。尽管层粘连蛋白A/C耗尽，但与LIV处理一样，层粘连蛋白A/C消耗显著降低了脂肪生成标志物（脂联素，细胞脂质含量）。在层粘连蛋白A/C缺失期间，响应机械挑战的局灶粘连磷酸化也得以保留。RNA-seq显示，LIV处理没有导致主要的脂肪生成转录组变化，这表明LIV对脂肪生成的调节可能不在转录水平上发生。我们观察到在lamin A/C耗尽和LIV过程中，干扰素信号被下调，这表明可能有共同的调节蛋白翻译的机制元件。我们得出结论，脂肪形成的机械调节和局灶黏附的机械激活的功能独立于层粘连蛋白A/C。
Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7.8
作者：
Chojnowski, Alexandre;Ong, Peh Fern;Dreesen, Oliver
通讯作者：
Dreesen, Oliver
影响因子：
3.7
作者：
Li, Wei;Yeo, Li Sze;Duque, Gustavo
通讯作者：
Duque, Gustavo
影响因子：
3.4
作者：
Lee, Jerry S. H.;Hale, Christopher M.;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
12.3
作者：
Kim D;Pertea G;Trapnell C;Pimentel H;Kelley R;Salzberg SL
通讯作者：
Salzberg SL