Elsevier

Stem Cell Research

Volume 17, Issue 2, September 2016, Pages 406-412
Stem Cell Research

Short report
A systems biology approach to identify niche determinants of cellular phenotypes

https://doi.org/10.1016/j.scr.2016.09.006Get rights and content
Under a Creative Commons license
open access

Highlights

  • Identification of sustained signaling that determines specific stem cell phenotype

  • Method for inference and ranking of niche determinants from gene expression data

  • Prediction of known and novel niche determinants of different stem cell systems

  • Potential applications in regenerative medicine

Abstract

Recent reports indicate a dominant role for cellular microenvironment or niche for stably maintaining cellular phenotypic states. Identification of key niche mediated signaling that maintains stem cells in specific phenotypic states remains a challenge, mainly due to the complex and dynamic nature of stem cell-niche interactions. In order to overcome this, we consider that stem cells maintain their phenotypic state by experiencing a constant effect created by the niche by integrating its signals via signaling pathways. Such a constant niche effect should induce sustained activation/inhibition of specific stem cell signaling pathways that controls the gene regulatory program defining the cellular phenotypic state. Based on this view, we propose a computational approach to identify the most likely receptor mediated signaling responsible for transmitting niche signals to the transcriptional regulatory network that maintain cell-specific gene expression patterns, termed as niche determinants. We demonstrate the utility of our method in different stem cell systems by identifying several known and novel niche determinants. Given the key role of niche in several degenerative diseases, identification of niche determinants can aid in developing strategies for potential applications in regenerative medicine.

Keywords

Stem cell niche
Signaling pathways
Transcriptional regulatory networks
Niche determinants

Cited by (0)

Author contributions: A.d.S. conceived and initiated the study. S.R. and S.M.A. collected data and performed initial analysis. S.R. and S.O. implemented the method. All authors interpreted the results and contributed for the drafting of the manuscript.