scholarly journals Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model

2021 ◽  
Vol 22 (18) ◽  
pp. 10098
Author(s):  
Francesca Paradiso ◽  
Stefano Serpelloni ◽  
Lewis W. Francis ◽  
Francesca Taraballi
Keyword(s):  
Cell Fate ◽  
Cancer Cell ◽  
Cell Types ◽  
3D Models ◽  
Mechanical Tests ◽  
Research Approach ◽  
3D Scaffold ◽  
Multicellular Spheroids ◽  
Multiple Cell ◽  
Third Dimension

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform’s level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements.

scholarly journals Emerging liver organoid platforms and technologies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Do Thuy Uyen Ha Lam ◽  
Yock Young Dan ◽  
Yun-Shen Chan ◽  
Huck-Hui Ng
Keyword(s):  
Cell Types ◽  
3D Models ◽  
Tissue Level ◽  
Patient Specific ◽  
Cell Culture Techniques ◽  
Culture Techniques ◽  
Cellular Models ◽  
Multiple Cell ◽  
Liver Organoids

AbstractBuilding human organs in a dish has been a long term goal of researchers in pursue of physiologically relevant models of human disease and for replacement of worn out and diseased organs. The liver has been an organ of interest for its central role in regulating body homeostasis as well as drug metabolism. An accurate liver replica should contain the multiple cell types found in the organ and these cells should be spatially organized to resemble tissue structures. More importantly, the in vitro model should recapitulate cellular and tissue level functions. Progress in cell culture techniques and bioengineering approaches have greatly accelerated the development of advance 3-dimensional (3D) cellular models commonly referred to as liver organoids. These 3D models described range from single to multiple cell type containing cultures with diverse applications from establishing patient-specific liver cells to modeling of chronic liver diseases and regenerative therapy. Each organoid platform is advantageous for specific applications and presents its own limitations. This review aims to provide a comprehensive summary of major liver organoid platforms and technologies developed for diverse applications.

The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4127-4138 ◽  
Author(s):  
Mirella Dottori ◽  
Michael K. Gross ◽  
Patricia Labosky ◽  
Martyn Goulding
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Winged Helix ◽  
Multiple Cell ◽  
Winged Helix Transcription Factor

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.

scholarly journals SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila

2002 ◽  
Vol 156 (4) ◽  
pp. 689-701 ◽  
Author(s):  
Jennifer A. Zallen ◽  
Yehudit Cohen ◽  
Andrew M. Hudson ◽  
Lynn Cooley ◽  
Eric Wieschaus ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Morphology ◽  
Actin Polymerization ◽  
Cell Types ◽  
Filamentous Actin ◽  
Cell Fate Decisions ◽  
Cytoplasmic Organization ◽  
Multiple Cell

The Arp2/3 complex and its activators, Scar/WAVE and Wiskott-Aldrich Syndrome protein (WASp), promote actin polymerization in vitro and have been proposed to influence cell shape and motility in vivo. We demonstrate that the Drosophila Scar homologue, SCAR, localizes to actin-rich structures and is required for normal cell morphology in multiple cell types throughout development. In particular, SCAR function is essential for cytoplasmic organization in the blastoderm, axon development in the central nervous system, egg chamber structure during oogenesis, and adult eye morphology. Highly similar developmental requirements are found for subunits of the Arp2/3 complex. In the blastoderm, SCAR and Arp2/3 mutations result in a reduction in the amount of cortical filamentous actin and the disruption of dynamically regulated actin structures. Remarkably, the single Drosophila WASp homologue, Wasp, is largely dispensable for these numerous Arp2/3-dependent functions, whereas SCAR does not contribute to cell fate decisions in which Wasp and Arp2/3 play an essential role. These results identify SCAR as a major component of Arp2/3-dependent cell morphology during Drosophila development and demonstrate that the Arp2/3 complex can govern distinct cell biological events in response to SCAR and Wasp regulation.

scholarly journals Inferring metabolic rewiring in embryonic neural development using single cell data

2020 ◽  
Author(s):  
Shashank Jatav ◽  
Saksham Malhotra ◽  
Freda D Miller ◽  
Abhishek Jha ◽  
Sidhartha Goyal
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Neural Development ◽  
Contextual Information ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Cell Level ◽  
Multiple Cell ◽  
Cell Data

AbstractMetabolism is intricately linked with cell fate changes. Much of this understanding comes from detailed metabolomics studies averaged across a population of cells which may be composed of multiple cell types. Currently, there are no quantitative techniques sensitive enough to assess metabolomics broadly at the single cell level. Here we present scMetNet, a technique that interrogates metabolic rewiring at the single cell resolution and we apply it to murine embryonic development. Our method first confirms the key metabolic pathways, categorized into bioenergetic, epigenetic and biosynthetic, that change as embryonic neural stem cells differentiate and age. It then goes beyond to identify specific sub-networks, such as the cholesterol and mevalonate biosynthesis pathway, that drive the global metabolic changes during neural cortical development. Having such contextual information about metabolic rewiring provides putative mechanisms driving stem cell differentiation and identifies potential targets for regulating neural stem cell and neuronal biology.

Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 906-915 ◽  
Author(s):  
Kristin Chadwick ◽  
Lisheng Wang ◽  
Li Li ◽  
Pablo Menendez ◽  
Barbara Murdoch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryoid Body ◽  
Embryonic Stem ◽  
Cell Types ◽  
Hematopoietic Differentiation ◽  
Multiple Cell ◽  
Hesc Lines

Abstract Human embryonic stem cells (hESCs) randomly differentiate into multiple cell types during embryoid body (EB) development. To date, characterization of specific factors capable of influencing hematopoietic cell fate from hESCs remains elusive. Here, we report that the treatment of hESCs during EB development with a combination of cytokines and bone morphogenetic protein-4 (BMP-4), a ventral mesoderm inducer, strongly promotes hematopoietic differentiation. Hematopoietic progenitors of multiple lineages were generated from EBs and were found to be restricted to the population of progeny expressing cell surface CD45. Addition of BMP-4 had no statistically significant effect on hematopoietic differentiation but enabled significant enhancement in progenitor self-renewal, independent of cytokine treatment. Hematopoietic commitment was characterized as the temporal emergence of single CD45+ cells first detectable after day 10 of culture and was accompanied by expression of hematopoietic transcription factors. Despite the removal of cytokines at day 10, hematopoietic differentiation of hESCs continued, suggesting that cytokines act on hematopoietic precursors as opposed to differentiated hematopoietic cells. Our study establishes the first evidence for the role of cytokines and BMP-4 in promoting hematopoietic differentiation of hESC lines and provides an unprecedented system to study early developmental events that govern the initiation of hematopoiesis in the human.

scholarly journals Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms

2021 ◽  
Vol 3 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Alexandra A. C. Newman ◽  
Vlad Serbulea ◽  
Richard A. Baylis ◽  
Laura S. Shankman ◽  
Xenia Bradley ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Cell Types ◽  
Fibrous Cap ◽  
Multiple Cell

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

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