P { margin-bottom: 0.21cm; direction: ltr; color: rgb(0, 0, 0); widows: 2; orphans: 2; }P.western { } Gene expression variability as a unifying element of the pluripotency network (#145)
Elizabeth A Mason
1
,
Jessica C Mar
2
,
Andrew Laslett
3
,
Martin Pera
4
,
John Quackenbush
5
,
Ernst Wolvetang
1
,
Christine A Wells
1
- AIBN, the University of Queensland, St Lucia, Brisbane, QLD, Australia
- The Albert Einstein College of Medicine, Bronx, New York, NY, USA
- Materials Science and Engineering, CSIRO, Clayton, VIC, Australia
- Centre for Neuroscience Research, University of Melbourne, Parkville, Melbourne, VIC, Australia
- Dana Farber Cancer Institute, Harvard University, Cambridge, Boston, MA, USA
The
term “pluripotent stem cell” encompasses a range of cellular
phenotypes, with the dual ability to self renew and generate cells of
the three embryonic germ layers. Phenotypic heterogeneity is a
hallmark of pluripotent stem cell populations, and is a function of
the oscillatory behaviour of Oct4 and Nanog, the master-regulators of
the pluripotency gene regulatory network. Here we present evidence
that variability in the expression of such genes provides a new
metric with which to characterize human pluripotent stem cell
populations. We conclude that even in homogenous populations, the
underlying genetic network displays high and low-variance elements.
We show that those genes with the least expression variability are
also highly connected, demonstrating a high level of regulatory
constraint of the core network elements. Oct4 and Nanog exhibit
different patterns of expression variability, indicating changes in
the stabilisation of expression of these key factors in different
stem cell phenotypes. Expression variability provides insight into
the heterogeneity of a pluripotent stem cell population, as well as
insight into the regulation of key network elements within a
well-defined pluripotency network.