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dc.contributor.authorSánchez-Luis
dc.contributor.authorJoaquín-García
dc.contributor.authorCampos-Laborie
dc.contributor.authorSánchez-Guijo
dc.contributor.authorRivas
dc.date.accessioned2020-04-06T23:05:06Z
dc.date.available2020-04-06T23:05:06Z
dc.date.issued2020-04-05
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304126
dc.description.abstractMesenchymal Stromal Cells (MSC) are multipotent cells characterized by self-renewal, multilineage differentiation, and immunomodulatory properties. To obtain a gene regulatory profile of human MSCs, we generated a compendium of more than two hundred cell samples with genome-wide expression data, including a homogeneous set of 93 samples of five related primary cell types: bone marrow mesenchymal stem cells (BM-MSC), hematopoietic stem cells (HSC), lymphocytes (LYM), fibroblasts (FIB), and osteoblasts (OSTB). All these samples were integrated to generate a regulatory gene network using the algorithm ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks; based on mutual information), that finds regulons (groups of target genes regulated by transcription factors) and regulators (i.e., transcription factors, TFs). Furtherly, the algorithm VIPER (Algorithm for Virtual Inference of Protein-activity by Enriched Regulon analysis) was used to inference protein activity and to identify the most significant TF regulators, which control the expression profile of the studied cells. Applying these algorithms, a footprint of candidate master regulators of BM-MSCs was defined, including the genes EPAS1, NFE2L1, SNAI2, STAB2, TEAD1, and TULP3, that presented consistent upregulation and hypomethylation in BM-MSCs. These TFs regulate the activation of the genes in the bone marrow MSC lineage and are involved in development, morphogenesis, cell differentiation, regulation of cell adhesion, and cell structure.
dc.languageen
dc.publisherMDPI
dc.subjectmesenchymal stromal cells
dc.subjecttranscription factor
dc.subjectregulons
dc.subjectmaster regulators
dc.subjectgene networks
dc.subjecttranscriptomics
dc.subjectbioinformatic
dc.subjectmeta-analysis
dc.titleDeciphering Master Gene Regulators and Associated Networks of Human Mesenchymal Stromal Cells
dc.typeArticle
dc.date.updated2020-04-06T23:05:06Z
prism.issueIdentifier4
prism.publicationNameBiomolecules
prism.volume10
dc.identifier.doi10.17863/CAM.51211
dcterms.dateAccepted2020-04-02
rioxxterms.versionofrecord10.3390/biom10040557
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2218-273X
pubs.funder-project-idInstituto de Salud Carlos III (PI18/00591)
pubs.funder-project-idHorizon 2020 Framework Programme (737390)


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