ORCID Profile
0000-0002-4697-595X
Current Organisation
UNSW Sydney
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Publisher: Wiley
Date: 22-02-2021
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.PBIOMOLBIO.2018.04.009
Abstract: The zebrafish (ZF) has become an essential model for biomedical, pharmacological and eco-toxicological heart research. Despite the anatomical differences between fish and human hearts, similarities in cellular structure and conservation of genes as well as pathways across vertebrates have led to an increase in the popularity of ZF as a model for human cardiac research. ZF research benefits from an entirely sequenced genome, which allows us to establish and study cardiovascular mutants to better understand cardiovascular diseases. In this review, we will discuss the importance of in vitro model systems for cardiac research and summarise results of in vitro 3D heart-like cell aggregates, consisting of myocardial tissue formed spontaneously from enzymatically digested whole embryonic ZF larvae (Zebrafish Heart Aggregate - ZFHA). We will give an overview of the similarities and differences of ZF versus human hearts and highlight why ZF complement established mammalian models (i.e. murine and large animal models) for cardiac research. At this stage, the ZFHA model system is being refined into a high-throughput (more ZFHA generated than larvae prepared) and stable in vitro test system to accomplish the same longevity of previously successful salmonid models. ZFHA have potential for the use of high-throughput-screenings of different factors like small molecules, nucleic acids, proteins and lipids which is difficult to achieve in the zebrafish in vivo screening models with lethal mutations as well as to explore ion channel disorders and to find appropriate drugs for safety screening.
Publisher: American Chemical Society (ACS)
Date: 16-08-2019
Publisher: Cold Spring Harbor Laboratory
Date: 28-10-2021
DOI: 10.1101/2021.10.28.466327
Abstract: Embryogenesis is orchestrated through local morphogen gradients and endometrial constraints that give rise to the three germ layers in a well-defined assembly. In vitro models of embryogenesis have been demonstrated by treating pluripotent stem cells in adherent or suspension culture with soluble morphogens and small molecules, which leads to tri-lineage differentiation. However, treatment with exogenous agents override the subtle spatiotemporal changes observed in vivo that ultimately underly the human body plan. Here we demonstrate how microconfinement of pluripotent stem cells on hydrogel substrates catalyses gastrulation-like events without the need for supplements. Within six hours of initial seeding, cells at the boundary show elevated cytoskeletal tension and yes-associated protein (YAP) activity, which leads to changes in cell and nuclear morphology, epithelial to mesenchymal transition, and emergence of defined patterns of primitive streak containing SRY-Box Transcription Factor 17 (SOX17) + T/BRACHYURY + cells. Immunofluorescence staining, transcript analysis, and the use of pharmacological modulators reveal a role for mechanotransduction-coupled non-canonical wingless-type (WNT) signalling in promoting epithelial to mesenchymal transition and multilayered organization within the colonies. These microscale gastruloids were removed from the substrate and encapsulated in 3D hydrogels, where biomaterials properties correspond to maintenance and spatial positioning of the primitive streak. Together, this approach demonstrates how materials alone can nurture embryonic gastrulation, thereby providing an in vitro model of early development.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jake Ireland.