Network based transcription factor analysis of regenerating axolotl limbs

Deepali Jhamb, Nandini Rao, Derek J. Milner, Fengyu Song, Jo Ann Cameron, David L. Stocum, Mathew J. Palakal

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Studies on amphibian limb regeneration began in the early 1700's but we still do not completely understand the cellular and molecular events of this unique process. Understanding a complex biological process such as limb regeneration is more complicated than the knowledge of the individual genes or proteins involved. Here we followed a systems biology approach in an effort to construct the networks and pathways of protein interactions involved in formation of the accumulation blastema in regenerating axolotl limbs.Results: We used the human orthologs of proteins previously identified by our research team as bait to identify the transcription factor (TF) pathways and networks that regulate blastema formation in amputated axolotl limbs. The five most connected factors, c-Myc, SP1, HNF4A, ESR1 and p53 regulate ~50% of the proteins in our data. Among these, c-Myc and SP1 regulate 36.2% of the proteins. c-Myc was the most highly connected TF (71 targets). Network analysis showed that TGF-β1 and fibronectin (FN) lead to the activation of these TFs. We found that other TFs known to be involved in epigenetic reprogramming, such as Klf4, Oct4, and Lin28 are also connected to c-Myc and SP1.Conclusions: Our study provides a systems biology approach to how different molecular entities inter-connect with each other during the formation of an accumulation blastema in regenerating axolotl limbs. This approach provides an in silico methodology to identify proteins that are not detected by experimental methods such as proteomics but are potentially important to blastema formation. We found that the TFs, c-Myc and SP1 and their target genes could potentially play a central role in limb regeneration. Systems biology has the potential to map out numerous other pathways that are crucial to blastema formation in regeneration-competent limbs, to compare these to the pathways that characterize regeneration-deficient limbs and finally, to identify stem cell markers in regeneration.

Original languageEnglish (US)
Article number80
JournalBMC Bioinformatics
Volume12
DOIs
StatePublished - Mar 18 2011
Externally publishedYes

Fingerprint

Ambystoma mexicanum
Transcription factors
Regeneration
Factor analysis
Factor Analysis
Transcription Factor
Statistical Factor Analysis
Transcription Factors
Extremities
Proteins
Protein
Pathway
Systems Biology
Genes
Fibronectin
Gene
Target
Stem Cells
Proteomics
Network Analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics
  • Structural Biology

Cite this

Jhamb, D., Rao, N., Milner, D. J., Song, F., Cameron, J. A., Stocum, D. L., & Palakal, M. J. (2011). Network based transcription factor analysis of regenerating axolotl limbs. BMC Bioinformatics, 12, [80]. https://doi.org/10.1186/1471-2105-12-80

Network based transcription factor analysis of regenerating axolotl limbs. / Jhamb, Deepali; Rao, Nandini; Milner, Derek J.; Song, Fengyu; Cameron, Jo Ann; Stocum, David L.; Palakal, Mathew J.

In: BMC Bioinformatics, Vol. 12, 80, 18.03.2011.

Research output: Contribution to journalArticle

Jhamb, D, Rao, N, Milner, DJ, Song, F, Cameron, JA, Stocum, DL & Palakal, MJ 2011, 'Network based transcription factor analysis of regenerating axolotl limbs', BMC Bioinformatics, vol. 12, 80. https://doi.org/10.1186/1471-2105-12-80
Jhamb D, Rao N, Milner DJ, Song F, Cameron JA, Stocum DL et al. Network based transcription factor analysis of regenerating axolotl limbs. BMC Bioinformatics. 2011 Mar 18;12. 80. https://doi.org/10.1186/1471-2105-12-80
Jhamb, Deepali ; Rao, Nandini ; Milner, Derek J. ; Song, Fengyu ; Cameron, Jo Ann ; Stocum, David L. ; Palakal, Mathew J. / Network based transcription factor analysis of regenerating axolotl limbs. In: BMC Bioinformatics. 2011 ; Vol. 12.
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