A systems biology approach to identify niche determinants of cellular phenotypes

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 o...

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Bibliographic Details
Published in:Stem cell research 2016-09, Vol.17 (2), p.406-412
Main Authors: Ravichandran, Srikanth, Okawa, Satoshi, Martínez Arbas, Susana, del Sol, Antonio
Format: Article
Language:English
Subjects:
Algorithms
Cell Differentiation
Gene Regulatory Networks
Hair Follicle - cytology
Hair Follicle - metabolism
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Humans
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Neurons - cytology
Neurons - metabolism
Niche determinants
Phenotype
Regenerative Medicine
Signal Transduction
Signaling pathways
Stem Cell Niche
Stem Cells - cytology
Stem Cells - metabolism
Transcriptional regulatory networks
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Summary: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. •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
ISSN:1873-5061
1876-7753
DOI:10.1016/j.scr.2016.09.006