Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells

Abstract

Background The cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive. Results We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role. Conclusions Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells, influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affecting pluripotency and cell fate.

Cluster-Assembled Zirconia Substrates Accelerate the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

“…Additionally, the nuclei roundness of bMSCs was increased after 24 h of culture on the nanostructured surface. Changes in nuclear morphology have been described in differentiating embryo stem cells and are related to the modulation of gene expression [38,39]. The remodeling of nuclear size and shape has been reported in the adipogenic differentiation of bMSCs [40], though this issue seems to be overlooked in osteogenic differentiation.…”

Genetic dissection of the pluripotent proteome through multi-omics data integration

“…We previously identified significant sex differences in gene expression stemming largely from X Chromosome dosage (Skelly et al, 2020), and here we find that these differences are carried through to the protein level (Schulz et al, 2014; Werner et al, 2017). Gene Set Variation Analysis (GSVA) identified multiple pluripotency and differentiation pathways that vary in activity across ESCs, including tRNA modification (Bornelöv et al, 2019); regulation of histone acetylation (Gonzales-Cope et al, 2016), intermediate filament organization (Romero et al, 2022), glutathione biosynthesis (Gu et al, 2016; Jagust et al, 2020; Xin et al, 2019), Golgi vesicle transport (Cruz et al, 2018), hippo signaling (Frum et al, 2018; Sun et al, 2020), and JUN kinase activation (Li et al, 2019) (Table S2). Of note, variation in these pathways is uniquely observed in the proteomics data.…”

Capturing Transitional Pluripotency through Proline Metabolism

“…Although naïve ESC-derived aggregates appear to be highly homogenous, round-shaped and compacted, PiCs generate loosely packed aggregates that are more irregular and disorganized [ 35 , 40 ]. Although a further analysis is needed, this phenotype may be explained, in part, by the heterogeneity of PiCs; only a fraction/subpopulation of PiCs might be able to engage in stable cell–cell interactions based on a cytoskeleton organization [ 73 ] and/or cell surface dynamics/fluctuations [ 63 ].…”