title: A systems biology approach to identify niche determinants of cellular phenotypes.
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.
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Ravichandran
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okawa
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
authors.forename: Susana
authors.initials: S
authors.lastname: Martínez Arbas
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg. Electronic address: antonio.delsol@uni.lu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Sol
mesh_terms: D000465:Algorithms; D002454:Cell Differentiation; D053263:Gene Regulatory Networks; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D044968:Regenerative Medicine; D015398:Signal Transduction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
keywords: Niche determinants; Signaling pathways; Stem cell niche; Transcriptional regulatory networks