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Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning.

eLife | 2018

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.

Pubmed ID: 29412136 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01DK084391
  • Agency: NICHD NIH HHS, United States
    Id: R01HD080699
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD080699
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD094868
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK084391
  • Agency: NCI NIH HHS, United States
    Id: P30CA008748
  • Agency: Wellcome Trust, United Kingdom

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This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

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Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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FISHER (tool)

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Cell line ES-R1 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)

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ES-E14 (cell line)

RRID:CVCL_C320

Cell line ES-E14 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)

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Crl:CD1(ICR) (organism)

RRID:IMSR_CRL:22

Mus musculus with name Crl:CD1(ICR) from IMSR.

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Ilastik (software resource)

RRID:SCR_015246

Tool for interactive image classification, segmentation and analysis, built as a modular software framework, which currently has workflows for automated (supervised) pixel- and object-level classification, automated and semi-automated object tracking, semi-automated segmentation and object counting without detection.

View all literature mentions

Oct3/4 Antibody (C-10) (antibody)

RRID:AB_628051

This monoclonal targets Oct-3/4

View all literature mentions

Human Otx2 Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2157172

This polyclonal targets Human Otx2 Affinity Purified Ab

View all literature mentions

Anti-Green Fluorescent Protein Antibody (antibody)

RRID:AB_10000240

This polyclonal targets Green Fluorescent Protein (GFP)

View all literature mentions

GATA-6 (D61E4) XP Rabbit mAb (antibody)

RRID:AB_10705521

This monoclonal targets GATA-6 (D61E4) XP Rabbit mAb

View all literature mentions

FOXA2 antibody [EPR4466] (antibody)

RRID:AB_11157157

This monoclonal targets FOXA2 antibody [EPR4466]

View all literature mentions

Anti-CDX-2, Clone CDX2-88 (antibody)

RRID:AB_2650531

This monoclonal targets CDX-2

View all literature mentions

N-cadherin (H-63) (antibody)

RRID:AB_647794

This polyclonal targets CDH2

View all literature mentions

Human/Mouse Brachyury Affinity Purified Polyclonal Ab (antibody)

RRID:AB_2200235

This polyclonal targets Human/Mouse Brachyury Affinity Purified Ab

View all literature mentions

46C (cell line)

RRID:CVCL_Y482

Cell line 46C is a Embryonic stem cell with a species of origin Mus musculus (Mouse)

View all literature mentions

ES-R1 (cell line)

RRID:CVCL_2167

Cell line ES-R1 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)

View all literature mentions

ES-E14 (cell line)

RRID:CVCL_C320

Cell line ES-E14 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)

View all literature mentions

Crl:CD1(ICR) (organism)

RRID:IMSR_CRL:22

Mus musculus with name Crl:CD1(ICR) from IMSR.

View all literature mentions