Functional relationships between genes associated with differentiation potential of aged myogenic progenitors
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1Division of Biomedical Informatics,
University of Arkansas for Medical Sciences,
USA
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2Statistical Center for HIV/AIDS Research and Prevention,
Fred Hutchinson Cancer Research Center,
USA
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3Department of Statistical Sciences,
University of Padova,
Italy
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4College of Public Health,
University of Arkansas for Medical Sciences,
USA
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5Department of Pediatrics,
University of Arkansas for Medical Sciences,
USA
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6College of Health Sciences,
University of Kentucky,
USA
Aging is accompanied by considerable heterogeneity with possible co-expression of differentiation pathways. The present study investigates the interplay between crucial myogenic, adipogenic and Wnt-related genes orchestrating aged myogenic progenitor differentiation (AMPD) using clonal gene expression profiling in conjunction with Bayesian structure learning (BSL) techniques. The expression of three myogenic regulatory factor genes (Myogenin, Myf-5, MyoD1), four genes involved in regulating adipogenic potential (C/EBPα, DDIT3, FoxC2, PPARγ), and two genes in the Wnt-signaling pathway (Lrp5, Wnt5a) known to influence both differentiation programs were determined across thirty-four clones by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Three control genes were used for normalization of the clonal expression data (18S, GAPDH and B2M). Constraint-based BSL techniques, namely (a) PC Algorithm, (b) Grow-shrink algorithm (GS), and (c) Incremental Association Markov Blanket (IAMB) were used to model the functional relationships (FRs) in the form of acyclic networks from the clonal expression profiles. A novel resampling approach that obviates the need for a user-defined confidence threshold is proposed to identify statistically significant FRs at small sample sizes. Interestingly, the resulting acyclic network consisted of FRs corresponding to myogenic, adipogenic, Wnt-related genes and their interaction. A significant number of these FRs were robust to normalization across the three house-keeping genes and the choice of the BSL technique. The results presented elucidate the delicate balance between differentiation pathways (i.e. myogenic as well as adipogenic) and possible cross-talk between pathways in AMPD.
Keywords :
aged myogenic progenitor differentiation,
Bayesian structure learning,
functional relationships
Citation
:
Nagarajan
R,
Datta
S,
Scutari
M,
Beggs
M,
Nolen
G and
Peterson
C
(2010). Functional relationships between genes associated with differentiation potential of aged myogenic progenitors.
Front. Physio. doi:10.3389/fphys.2010.00021
Received
:
23 Mar 2010;
Accepted:
23 Jun 2010.
Edited by
:
Michael L. Johnson, University of Virginia, USA
Reviewed by
:
Aaron J. Mackey, The Ohio State University, USA
Guanghui Hu, Hong Kong Baptist University, Hong Kong
Copyright
: ©
2010
Nagarajan,
Datta,
Scutari,
Beggs,
Nolen and
Peterson.
This is an open-access publication subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*
Correspondence
:
Dr.
Radhakrishnan
Nagarajan, University of Arkansas for Medical Sciences, Division of Biomedical Informatics, Little Rock, AR, USA, rnagarajan@uams.edu