scholarly journals Precision Surface Microtopography Regulates Cell Fate via Changes to Actomyosin Contractility and Nuclear Architecture

2021 ◽  
pp. 2003186
Author(s):  
James Carthew ◽  
Hazem H. Abdelmaksoud ◽  
Margeaux Hodgson‐Garms ◽  
Stella Aslanoglou ◽  
Sara Ghavamian ◽  
...  
Keyword(s):  
Cell Fate ◽  
Nuclear Architecture ◽  
Surface Microtopography ◽  
Actomyosin Contractility

scholarly journals Chromatin Reprogramming via Contact Guidance-Induced Nuclear Deformation Promotes Stem Cell Differentiation

2021 ◽  
Author(s):  
Xinlong Wang ◽  
Vasundhara Agrawal ◽  
Yue Li ◽  
Ranya Virk ◽  
Priyam Patel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Nuclear Architecture ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation ◽  
Contact Guidance ◽  
Live Cells ◽  
Nuclear Deformation ◽  
Chromatin Reprogramming

Abstract Efficient manipulation of cell fate is important for regenerative engineering applications. Lineage-specific differentiation of stem cells is particularly challenging due to their inherent plasticity. Engineered topographies may alter cellular plasticity through contact guidance. However, the ability to rationally design topographies to regulate phenotypic outcomes has been hindered in part by the lack of tools to quantify nanoscale chromatin structure reorganization in live cells. Herein we use micropillars, molecular, and nanostructural quantification tools to investigate how nuclear morphology in human mesenchymal stem cells (hMSCs) affects chromatin conformation and osteogenic differentiation. We show that micropillar-induced contact guidance is transduced via the cytoskeleton and impacts nuclear architecture, lamin A/C multimerization, histone modifications, and the 3-D conformation of chromatin within packing domains, a key regulator of transcriptional responsiveness. Micropillars repressed expression of genes associated with developmental processes and enhanced lineage-specific responsiveness, thereby decreasing cell plasticity and off-target differentiation, and facilitating osteogenic differentiation of hMSCs. Altogether, these findings reveal that chromatin reprogramming through contact guidance-induced nuclear deformation can be an efficient way to manipulate cell fate.

scholarly journals Asymmetric Inheritance of Cell Fate Determinants: Focus on RNA

2019 ◽  
Vol 5 (2) ◽  
pp. 38 ◽  
Author(s):  
Yelyzaveta Shlyakhtina ◽  
Katherine L. Moran ◽  
Maximiliano M. Portal
Keyword(s):  
Cell Fate ◽  
Mammalian Cells ◽  
High Throughput Sequencing ◽  
General Pattern ◽  
Nuclear Architecture ◽  
Biological Information ◽  
Current Evidence ◽  
Rna Molecules ◽  
Sequencing Technologies ◽  
Wide Range

During the last decade, and mainly primed by major developments in high-throughput sequencing technologies, the catalogue of RNA molecules harbouring regulatory functions has increased at a steady pace. Current evidence indicates that hundreds of mammalian RNAs have regulatory roles at several levels, including transcription, translation/post-translation, chromatin structure, and nuclear architecture, thus suggesting that RNA molecules are indeed mighty controllers in the flow of biological information. Therefore, it is logical to suggest that there must exist a series of molecular systems that safeguard the faithful inheritance of RNA content throughout cell division and that those mechanisms must be tightly controlled to ensure the successful segregation of key molecules to the progeny. Interestingly, whilst a handful of integral components of mammalian cells seem to follow a general pattern of asymmetric inheritance throughout division, the fate of RNA molecules largely remains a mystery. Herein, we will discuss current concepts of asymmetric inheritance in a wide range of systems, including prions, proteins, and finally RNA molecules, to assess overall the biological impact of RNA inheritance in cellular plasticity and evolutionary fitness.

scholarly journals Epigenetic remodeling during monolayer cell expansion reduces therapeutic potential

2021 ◽  
Author(s):  
Adrienne Scott ◽  
Eduard Casas ◽  
Stephanie Ellyse Schneider ◽  
Alison Swearingen ◽  
Courtney Van Den Elzen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Expansion ◽  
Therapeutic Potential ◽  
Three Dimensional ◽  
3D Culture ◽  
Nuclear Architecture ◽  
Large Cell ◽  
Chondrocyte Phenotype ◽  
Epigenetic Remodeling ◽  
Mechanical Memory

Understanding how cells remember previous mechanical environments to influence their fate, or mechanical memory, informs the design of biomaterials and therapies in medicine. Current regeneration therapies require two-dimensional (2D) cell expansion processes to achieve large cell populations critical for the repair of damaged (e.g. connective and musculoskeletal) tissues. However, the influence of mechanical memory on cell fate following expansion is unknown, and mechanisms defining how physical environments influence the therapeutic potential of cells remain poorly understood. Here, we show that the organization of histone H3 trimethylated at lysine 9 (H3K9me3) and expression of tissue-identifying genes in primary cartilage cells (chondrocytes) transferred to three-dimensional (3D) hydrogels depends on the number of previous population doublings on tissue culture plastic during 2D cell expansion. Decreased levels of H3K9me3 occupying promoters of dedifferentiation genes after the 2D culture were also retained in 3D culture. Suppression of H3K9me3 during expansion of cells isolated from a murine model similarly resulted in the loss of the chondrocyte phenotype and global remodeling of nuclear architecture. In contrast, increasing levels of H3K9me3 through inhibiting H3K9 demethylases partially rescued the chondrogenic nuclear architecture and gene expression, which has important implications for tissue repair therapies, where expansion of large numbers of phenotypically-suitable cells is required. Overall, our findings indicate mechanical memory in primary cells is encoded in the chromatin architecture, which impacts cell fate and the phenotype of expanded cells.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

Centromere assembly and non-random sister chromatid segregation in stem cells

2020 ◽  
Vol 64 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Ben L. Carty ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Sister Chromatid ◽  
Asymmetric Cell Division ◽  
Protein A ◽  
Germline Stem Cells ◽  
Sister Chromatids ◽  
Centromere Protein A ◽  
Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

Molecular regulation of brown and beige fat cell fate

2014 ◽  
Author(s):  
Patrick Seale ◽  
Wenshan Wang ◽  
Sona Rajakumari ◽  
Matthew Harms
Keyword(s):  
Cell Fate ◽  
Molecular Regulation ◽  
Fat Cell ◽  
Beige Fat

Use of Flexible Materials with a Novel Pressure Driven Equibiaxial Cell Stretching Device for Mechanical Stimulation of Single Mammalian Cells

2003 ◽  
Vol 773 ◽  
Author(s):  
James D. Kubicek ◽  
Stephanie Brelsford ◽  
Philip R. LeDuc
Keyword(s):  
Cell Fate ◽  
Mechanical Stimulation ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Single Cells ◽  
Complex Nature ◽  
Cellular Behavior ◽  
Cell Stretching ◽  
Stimulation Of ◽  
Pressure Driven

AbstractMechanical stimulation of single cells has been shown to affect cellular behavior from the molecular scale to ultimate cell fate including apoptosis and proliferation. In this, the ability to control the spatiotemporal application of force on cells through their extracellular matrix connections is critical to understand the cellular response of mechanotransduction. Here, we develop and utilize a novel pressure-driven equibiaxial cell stretching device (PECS) combined with an elastomeric material to control specifically the mechanical stimulation on single cells. Cells were cultured on silicone membranes coated with molecular matrices and then a uniform pressure was introduced to the opposite surface of the membrane to stretch single cells equibiaxially. This allowed us to apply mechanical deformation to investigate the complex nature of cell shape and structure. These results will enhance our knowledge of cellular and molecular function as well as provide insights into fields including biomechanics, tissue engineering, and drug discovery.

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