A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells

Hough, Shelley R., Laslett, Andrew L., Grimmond, Sean B., Kolle, Gabriel and Pera, Martin F. (2009) A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells. PLoS One, 4 11: x-x. doi:10.1371/journal.pone.0007708

Author Hough, Shelley R.
Laslett, Andrew L.
Grimmond, Sean B.
Kolle, Gabriel
Pera, Martin F.
Title A continuum of cell states spans pluripotency and lineage commitment in human embryonic stem cells
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2009-11
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.pone.0007708
Open Access Status DOI
Volume 4
Issue 11
Start page x
End page x
Total pages 10
Editor Thomas A Reh
Place of publication San Francisco, CA
Publisher Public Library of Science
Collection year 2010
Language eng
Subject C1
920102 Cancer and Related Disorders
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Formatted abstract
Background: Commitment in embryonic stem cells is often depicted as a binary choice between alternate cell states,
pluripotency and specification to a particular germ layer or extraembryonic lineage. However, close examination of human
ES cell cultures has revealed significant heterogeneity in the stem cell compartment.
Methodology/Principal Findings: We isolated subpopulations of embryonic stem cells using surface markers, then
examined their expression of pluripotency genes and lineage specific transcription factors at the single cell level, and tested
their ability to regenerate colonies of stem cells. Transcript analysis of single embryonic stem cells showed that there is a
gradient and a hierarchy of expression of pluripotency genes in the population. Even cells at the top of the hierarchy
generally express only a subset of the stem cell genes studied. Many cells co-express pluripotency and lineage specific
genes. Cells along the continuum show a progressively decreasing likelihood of self renewal as their expression of stem cell
surface markers and pluripotency genes wanes. Most cells that are positive for stem cell surface markers express Oct-4, but
only those towards the top of the hierarchy express the nodal receptor TDGF-1 and the growth factor GDF3.
Significance: These findings on gene expression in single embryonic stem cells are in concert with recent studies of early
mammalian development, which reveal molecular heterogeneity and a stochasticity of gene expression in blastomeres.
Our work indicates that only a small fraction of the population resides at the top of the hierarchy, that lineage priming
(co-expression of stem cell and lineage specific genes) characterizes pluripotent stem cell populations, and that extrinsic
signaling pathways are upstream of transcription factor networks that control pluripotency.
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Article number: e7708

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 73 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 12 Feb 2010, 12:02:44 EST by Susan Allen on behalf of Institute for Molecular Bioscience