Functional relationships between genes associated with differentiation potential of aged myogenic progenitors
Division of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Department of Statistical Sciences, University of Padova, Padova, Italy
College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
College of Health Sciences, University of Kentucky, Lexington, KY, 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 34 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 (GS) algorithm, 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.
functional relationships, aged myogenic progenitor differentiation, Bayesian structure learning
Nagarajan R, Datta S, Scutari M, Beggs ML, Nolen GT and Peterson CA (2010) Functional relationships between genes associated with differentiation potential of aged myogenic progenitors. Front. Physiology 1:21. doi: 10.3389/fphys.2010.00021
Received: 23 March 2010;
Paper pending published: 03 May 2010;
Accepted: 23 June 2010;
Published online: 09 September 2010.
Aaron J. Mackey
, The Ohio State University, USA
Guanghui Hu, Hong Kong Baptist University, Hong Kong
© 2010 Nagarajan, Datta, Scutari, Beggs, Nolen and Peterson. This is an open-access article 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.
Radhakrishnan Nagarajan, Division of Biomedical Informatics, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 781, Little Rock, AR 72205, USA. e-mail: email@example.com