Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the h...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2018-02-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/32839 |
id |
doaj-8eea50c5e0f14b07bca739e2f1420f10 |
---|---|
record_format |
Article |
spelling |
doaj-8eea50c5e0f14b07bca739e2f1420f102021-05-05T15:35:22ZengeLife Sciences Publications LtdeLife2050-084X2018-02-01710.7554/eLife.32839Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterningSophie M Morgani0https://orcid.org/0000-0002-4290-1080Jakob J Metzger1Jennifer Nichols2Eric D Siggia3https://orcid.org/0000-0001-7482-1854Anna-Katerina Hadjantonakis4https://orcid.org/0000-0002-7580-5124Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States; Wellcome Trust-Medical Research Council Centre for Stem Cell Research, University of Cambridge, Cambridge, United KingdomCenter for Studies in Physics and Biology, The Rockefeller University, New York, United StatesWellcome Trust-Medical Research Council Centre for Stem Cell Research, University of Cambridge, Cambridge, United KingdomCenter for Studies in Physics and Biology, The Rockefeller University, New York, United StatesDevelopmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United StatesDuring gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.https://elifesciences.org/articles/32839mammalian Embryoepiblastgastrulationpluripotent stem cellsmicropatterns |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie M Morgani Jakob J Metzger Jennifer Nichols Eric D Siggia Anna-Katerina Hadjantonakis |
spellingShingle |
Sophie M Morgani Jakob J Metzger Jennifer Nichols Eric D Siggia Anna-Katerina Hadjantonakis Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning eLife mammalian Embryo epiblast gastrulation pluripotent stem cells micropatterns |
author_facet |
Sophie M Morgani Jakob J Metzger Jennifer Nichols Eric D Siggia Anna-Katerina Hadjantonakis |
author_sort |
Sophie M Morgani |
title |
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
title_short |
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
title_full |
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
title_fullStr |
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
title_full_unstemmed |
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
title_sort |
micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-02-01 |
description |
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species. |
topic |
mammalian Embryo epiblast gastrulation pluripotent stem cells micropatterns |
url |
https://elifesciences.org/articles/32839 |
work_keys_str_mv |
AT sophiemmorgani micropatterndifferentiationofmousepluripotentstemcellsrecapitulatesembryoregionalizedcellfatepatterning AT jakobjmetzger micropatterndifferentiationofmousepluripotentstemcellsrecapitulatesembryoregionalizedcellfatepatterning AT jennifernichols micropatterndifferentiationofmousepluripotentstemcellsrecapitulatesembryoregionalizedcellfatepatterning AT ericdsiggia micropatterndifferentiationofmousepluripotentstemcellsrecapitulatesembryoregionalizedcellfatepatterning AT annakaterinahadjantonakis micropatterndifferentiationofmousepluripotentstemcellsrecapitulatesembryoregionalizedcellfatepatterning |
_version_ |
1721459921209262080 |