Mechanoresponses in mesenchymal stem cells (MSCs) guide both differentiation and function. In this review, we focus on advances in0 our understanding of how the cytoplasmic cytoskeleton, nuclear envelope and nucleoskeleton, which are connected via LINC () complexes, are emerging as an integrated dynamic signaling platform to regulate MSC mechanobiology. This dynamic interconnectivity affects mechanical signaling and transfer of signals into the nucleus. In this way, nuclear and LINC-mediated cytoskeletal connectivity play a critical role in maintaining mechanical signaling that affects MSC fate by serving as both mechanosensory and mechanoresponsive structures. We review disease and age related compromises of LINC complexes and nucleoskeleton that contribute to the etiology of musculoskeletal diseases. Finally we invite the idea that acquired dysfunctions of LINC might be a contributing factor to conditions such as aging, microgravity and osteoporosis and discuss potential mechanical strategies to modulate LINC connectivity to combat these conditions.
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http://dx.doi.org/10.1007/s40610-016-0032-8 | DOI Listing |
Sci Rep
December 2024
BioSpyder Technologies, Inc., Carlsbad, CA, USA.
We report the development and performance of a novel genomics platform, TempO-LINC, for conducting high-throughput transcriptomic analysis on single cells and nuclei. TempO-LINC works by adding cell-identifying molecular barcodes onto highly selective and high-sensitivity gene expression probes within fixed cells, without having to first generate cDNA. Using an instrument-free combinatorial indexing approach, all probes within the same fixed cell receive an identical barcode, enabling the reconstruction of single-cell gene expression profiles across as few as several hundred cells and up to 100,000 + cells per sample.
View Article and Find Full Text PDFMol Biol Cell
December 2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the Hook homolog ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.
View Article and Find Full Text PDFCell Prolif
December 2024
Department of Orthodontics, Faculty of Medicine, Justus Liebig University, Giessen, Germany.
Cellular mechanotransduction is a complex physiological process that integrates alterations in the external environment with cellular behaviours. In recent years, the role of the nucleus in mechanotransduction has gathered increased attention. Our research investigated the involvement of lamin A/C, a component of the nuclear envelope, in the mechanotransduction of macrophages under compressive force.
View Article and Find Full Text PDFCells
December 2024
Department of Biosciences, Durham University, Durham DH1 3LE, UK.
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterised by the absence of targetable hormone receptors and increased metastatic rates. As nuclear softening strongly contributes to TNBC's enhanced metastatic capacity, increasing the nuclear stiffness of TNBC cells may present a promising therapeutic avenue. Previous evidence has demonstrated the ability of Sirtuin 2 (SIRT2) inhibition to induce cytoskeletal reorganisation, a key factor in regulating nuclear mechanics.
View Article and Find Full Text PDFMitosis in eukaryotes involves reorganization of the nuclear envelope (NE) and microtubule-organizing centres (MTOCs). In , the causative agent of malaria, male gametogenesis mitosis is exceptionally rapid and divergent. Within 8 minutes, the haploid male gametocyte genome undergoes three replication cycles (1N to 8N), while maintaining an intact NE.
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