title: Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells.
abstract: Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterization of their cell-surface interface limits their clinical exploitation. We have employed subcellular fractionation with quantitative discovery proteomics to define the cell-surface interface proteome of human bone marrow mesenchymal stromal/stem cells (MSCs) and human umbilical cord perivascular cells (HUCPVCs). We compared cell-surface-enriched fractions from MSCs and HUCPVCs (three donors each) with adult mesenchymal fibroblasts using eight-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6,000 proteins with high confidence. This approach identified 186 upregulated mesenchymal progenitor biomarkers. Validation of 10 of these markers, including ROR2, EPHA2, and PLXNA2, confirmed upregulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration, and differentiation. Our approach has delivered a cell-surface proteome repository that now enables improved selection and characterization of human mesenchymal progenitor populations.
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Rebecca J
authors: RJ
authors: Holley
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Guangping
authors: G
authors: Tai
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Andrew J K
authors: AJ
authors: Williamson
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Samuel
authors: S
authors: Taylor
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Stuart A
authors: SA
authors: Cain
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Stephen M
authors: SM
authors: Richardson
authors: Faculty of Engineering and Physical Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Catherine L R
authors: CL
authors: Merry
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
authors: Anthony D
authors: AD
authors: Whetton
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: cay.kielty@manchester.ac.uk.
authors: Cay M
authors: CM
authors: Kielty
authors: Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK. Electronic address: ann.canfield@manchester.ac.uk.
authors: Ann E
authors: AE
authors: Canfield
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism*; D015415:Biomarkers; D019070:Cell Lineage / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D020543:Proteome; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015203:Reproducibility of Results; D055153:Stem Cell Niche; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D020543:Proteome; D034741:RNA, Small Interfering