Heterogeneous lineage marker expression in naive embryonic stem cells is mostly due to spontaneous differentiation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08-21

AUTHORS

Gautham Nair, Elsa Abranches, Ana M. V. Guedes, Domingos Henrique, Arjun Raj

ABSTRACT

Populations of cultured mouse embryonic stem cells (ESCs) exhibit a subfraction of cells expressing uncharacteristically low levels of pluripotency markers such as Nanog. Yet, the extent to which individual Nanog-negative cells are differentiated, both from ESCs and from each other, remains unclear. Here, we show the transcriptome of Nanog-negative cells exhibits expression of classes of genes associated with differentiation that are not yet active in cells exposed to differentiation conditions for one day. Long non-coding RNAs, however, exhibit more changes in expression in the one-day-differentiated cells than in Nanog-negative cells. These results are consistent with the concept that Nanog-negative cells may contain subpopulations of both lineage-primed and differentiated cells. Single cell analysis showed that Nanog-negative cells display substantial and coherent heterogeneity in lineage marker expression in progressively nested subsets of cells exhibiting low levels of Nanog, then low levels of Oct4 and then a set of lineage markers, which express intensely in a small subset of these more differentiated cells. Our results suggest that the observed enrichment of lineage-specific marker gene expression in Nanog-negative cells is associated with spontaneous differentiation of a subset of these cells rather than the more random expression that may be associated with reversible lineage priming. More... »

PAGES

13339

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep13339

DOI

http://dx.doi.org/10.1038/srep13339

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002081078

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26292941


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