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Neuro-mesodermal progenitors (NMPs): a comparative study between pluripotent stem cells and embryo-derived populations.

Accepted version
Peer-reviewed

Type

Article

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Authors

Hayward, Penelope 
Martinez Arias, Alfonso  ORCID logo  https://orcid.org/0000-0002-1781-564X

Abstract

The mammalian embryo's caudal lateral epiblast (CLE) harbours bipotent progenitors, called neural mesodermal progenitors (NMPs), that contribute to the spinal cord and the paraxial mesoderm throughout axial elongation. Here, we performed a single cell analysis of different in vitro NMP populations produced either from embryonic stem cells (ESCs) or epiblast stem cells (EpiSCs) and compared them with E8.25 CLE mouse embryos. In our analysis of this region, our findings challenge the notion that NMPs can be defined by the exclusive co-expression of Sox2 and T at mRNA level. We analyse the in vitro NMP-like populations using a purpose-built support vector machine (SVM) based on the embryo CLE and use it as a classification model to compare the in vivo and in vitro populations. Our results show that NMP differentiation from ESCs leads to heterogeneous progenitor populations with few NMP-like cells, as defined by the SVM algorithm, whereas starting with EpiSCs yields a high proportion of cells with the embryo NMP signature. We find that the population from which the Epi-NMPs are derived in culture contains a node-like population, which suggests that this population probably maintains the expression of T in vitro and thereby a source of NMPs. In conclusion, differentiation of EpiSCs into NMPs reproduces events in vivo and suggests a sequence of events for the emergence of the NMP population.

Description

Keywords

Neuromesodermal progenitors, Single cells, Transcription, Animals, Body Patterning, Cell Differentiation, Cell Lineage, Embryo, Mammalian, Embryonic Stem Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Developmental, Germ Layers, Green Fluorescent Proteins, In Vitro Techniques, Male, Mesoderm, Mice, Neural Stem Cells, Pluripotent Stem Cells, Spinal Cord, Stem Cells, Support Vector Machine, Transcriptome

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)
Wellcome Trust (103392/Z/13/Z)
Medical Research Council (MC_PC_12009)
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