title: Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes.
abstract: Bone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis of functional markers for BMSC subsets. All clones expressed typical BMSC cell-surface antigens; however, clones with trilineage differentiation capacity exhibited enhanced vascular interaction gene sets, whereas non-differentiating clones were uniquely CD317 positive with significantly enriched immunomodulatory transcriptional networks and high IL-7 production. IL-7 lineage tracing and CD317 immunolocalization confirmed the existence of a rare non-differentiating BMSC subtype, distinct from Cxcl12-DsRed(+) perivascular stromal cells in vivo. Colony-forming CD317(+) IL-7(hi) cells, identified at ∼ 1%-3% frequency in heterogeneous human BMSC fractions, were found to have the same biomolecular profile as non-differentiating BMSC clones using Raman spectroscopy. Distinct functional identities can be assigned to BMSC subpopulations, which are likely to have specific roles in immune control, lymphopoiesis, and bone homeostasis.
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: James
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: James
authors.initials: J
authors.lastname: Fox
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Farinaz
authors.initials: F
authors.lastname: Afsari
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Clough
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Knight
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: James
authors.initials: J
authors.lastname: Ashmore
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ashton
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Olivier
authors.initials: O
authors.lastname: Preham
authors.affiliation: Erasmus Medical Centre, Dr. Molewaterplein 50, Rotterdam 3015 GE, the Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Hoogduijn
authors.affiliation: Department of Physics, University of York, York YO10 5DD, UK.
authors.forename: Raquel De Almeida Rocha
authors.initials: Rde A
authors.lastname: Ponzoni
authors.affiliation: Department of Physics, University of York, York YO10 5DD, UK; York Centre for Complex Systems Analysis, University of York, York YO10 5GE, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Hancock
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Coles
authors.affiliation: Department of Biology, University of York, York YO10 5DD, UK. Electronic address: paul.genever@york.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Genever
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D058948:Cell Tracking; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D016000:Cluster Analysis; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D054377:Chemokine CXCL12; D058851:GPI-Linked Proteins; D015851:Interleukin-7; D019098:Telomerase; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C515255:CXCL12 protein, human; C508605:IL7 protein, human; C509186:TERT protein, human