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An epiblast stem cell-derived multipotent progenitor population for axial extension.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Hayward, Penny 
Baillie-Johnson, Peter 
Steventon, Benjamin J 
Martinez Arias, Alfonso  ORCID logo  https://orcid.org/0000-0002-1781-564X

Abstract

The caudal lateral epiblast of mammalian embryos harbours bipotent progenitors that contribute to the spinal cord and the paraxial mesoderm in concert with the body axis elongation. These progenitors, called neural mesodermal progenitors (NMPs), are identified as cells that co-express Sox2 and T/brachyury, a criterion used to derive NMP-like cells from embryonic stem cells in vitro However, unlike embryonic NMPs, these progenitors do not self-renew. Here, we find that the protocols that yield NMP-like cells in vitro initially produce a multipotent population that, in addition to NMPs, generates progenitors for the lateral plate and intermediate mesoderm. We show that epiblast stem cells (EpiSCs) are an effective source of these multipotent progenitors, which are further differentiated by a balance between BMP and Nodal signalling. Importantly, we show that NMP-like cells derived from EpiSCs exhibit limited self-renewal in vitro and a gene expression signature like their embryonic counterparts.

Description

Keywords

Axial extension, Embryonic stem cells, Mammalian development, Neuromesodermal progenitors, Animals, Body Patterning, Cell Differentiation, Cell Lineage, Germ Layers, Mesoderm, Neural Stem Cells, SOXB1 Transcription Factors

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

146

Publisher

The Company of Biologists

Rights

All rights reserved
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M023370/1)
Biotechnology and Biological Sciences Research Council (BB/P003184/1)
EPSRC (1359454)
Engineering and Physical Sciences Research Council (EP/K503009/1)
Engineering and Physical Sciences Research Council (EP/L504920/1)
Wellcome Trust (109408/Z/15/Z)
Cambridge Trusts, Cambridge philosophical Society