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Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells

Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, a...

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Autores principales: van den Brink, Susanne C., Baillie-Johnson, Peter, Balayo, Tina, Hadjantonakis, Anna-Katerina, Nowotschin, Sonja, Turner, David A., Martinez Arias, Alfonso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302915/
https://www.ncbi.nlm.nih.gov/pubmed/25371360
http://dx.doi.org/10.1242/dev.113001
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author van den Brink, Susanne C.
Baillie-Johnson, Peter
Balayo, Tina
Hadjantonakis, Anna-Katerina
Nowotschin, Sonja
Turner, David A.
Martinez Arias, Alfonso
author_facet van den Brink, Susanne C.
Baillie-Johnson, Peter
Balayo, Tina
Hadjantonakis, Anna-Katerina
Nowotschin, Sonja
Turner, David A.
Martinez Arias, Alfonso
author_sort van den Brink, Susanne C.
collection PubMed
description Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call ‘gastruloids’.
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spelling pubmed-43029152015-01-29 Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells van den Brink, Susanne C. Baillie-Johnson, Peter Balayo, Tina Hadjantonakis, Anna-Katerina Nowotschin, Sonja Turner, David A. Martinez Arias, Alfonso Development Stem Cells and Regeneration Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call ‘gastruloids’. The Company of Biologists 2014-11-15 /pmc/articles/PMC4302915/ /pubmed/25371360 http://dx.doi.org/10.1242/dev.113001 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Stem Cells and Regeneration
van den Brink, Susanne C.
Baillie-Johnson, Peter
Balayo, Tina
Hadjantonakis, Anna-Katerina
Nowotschin, Sonja
Turner, David A.
Martinez Arias, Alfonso
Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title_full Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title_fullStr Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title_full_unstemmed Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title_short Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
title_sort symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells
topic Stem Cells and Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302915/
https://www.ncbi.nlm.nih.gov/pubmed/25371360
http://dx.doi.org/10.1242/dev.113001
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