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Title: | Haematopoietic development and HSC formation in vitro: promise and limitations of gastruloid models |
Authors: | Dijkhuis, L Johns, A Ragusa, D van den Brink, S Pina, C |
Keywords: | Gastruloid models;haematopoietic stem cells;pluripotent stem cells |
Issue Date: | 27-Dec-2023 |
Publisher: | Portland Press on behalf of the Biochemical Society |
Citation: | Dijkhuis, L. et al. (2024) ‘M-FISH evaluation of chromosome aberrations to examine for historical exposure to ionising radiation due to participation at British nuclear test sites’ in Journal of Radiological Protection, 7 (4), pp. 439 - 454. doi: 10.1042/ETLS20230091. |
Abstract: | Haematopoietic stem cells (HSCs) are the most extensively studied adult stem cells. Yet, six decades after their first description, reproducible and translatable generation of HSC in vitro remains an unmet challenge. HSC production in vitro is confounded by the multi-stage nature of blood production during development. Specification of HSC is a late event in embryonic blood production and depends on physical and chemical cues which remain incompletely characterised. The precise molecular composition of the HSC themselves is incompletely understood, limiting approaches to track their origin in situ in the appropriate cellular, chemical and mechanical context. Embryonic material at the point of HSC emergence is limiting, highlighting the need for an in vitro model of embryonic haematopoietic development in which current knowledge gaps can be addressed and exploited to enable HSC production. Gastruloids are pluripotent stem cell-derived 3-dimensional (3D) cellular aggregates which recapitulate developmental events in gastrulation and early organogenesis with spatial and temporal precision. Gastruloids self-organise multi-tissue structures upon minimal and controlled external cues, and are amenable to live imaging, screening, scaling and physicochemical manipulation to understand and translate tissue formation. In this review, we consider the haematopoietic potential of gastruloids and review early strategies to enhance blood progenitor and HSC production. We highlight possible strategies to achieve HSC production from gastruloids, and discuss the potential of gastruloid systems in illuminating current knowledge gaps in HSC specification. |
URI: | https://bura.brunel.ac.uk/handle/2438/27829 |
DOI: | https://doi.org/10.1042/ETLS20230091 |
ISSN: | 2397-8554 |
Other Identifiers: | ORCiD: Cristina Pina https://orcid.org/0000-0002-2575-6301 ORCiD: Denise Ragusa https://orcid.org/0000-0002-0303-8683 ORCiD: Susanne Carina van den Brink https://orcid.org/0000-0003-3683-7737 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 2023 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology and distributed under the Creative Commons Attribution License 4.0 (CC BY). | 2.51 MB | Adobe PDF | View/Open |
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