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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Company of Biologists
2014
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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’. |
format | Online Article Text |
id | pubmed-4302915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
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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