Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells

Rebecca J. Holley; Guangping Tai; Andrew J. K. Williamson; Samuel Taylor; Stuart Cain; Stephen M. Richardson; Catherine L. R. Merry; Anthony D. Whetton; Ann E. Canfield

doi:10.1016/j.stemcr.2015.01.007

Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells

Rebecca J. Holley, Guangping Tai, Andrew J. K. Williamson, Samuel Taylor, Stuart Cain, Stephen M. Richardson, Catherine L. R. Merry, Anthony D. Whetton, Ann E. Canfield

SoSS Research Centres

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Abstract

Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterisation 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 (3 donors each) with adult mesenchymal fibroblasts using 8-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6000 proteins with high confidence. This approach identified 186 up-regulated proteins as mesenchymal progenitor biomarkers. Validation of 10 of these cell surface markers, including ROR2, EPHA2and PLXNA2, confirmed up-regulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration and differentiation. Thus cell surface protein enrichment plus isobaric-tag labelling prior to MS has delivered a comprehensive cell surface proteome repository that now enables improved selection and functional characterisation of human mesenchymal progenitor populations.

Original language	English
Article number	25684225
Pages (from-to)	473-488
Number of pages	15
Journal	Stem Cell Reports
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2015.01.007
Publication status	Published - 10 Mar 2015

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@article{a7fd52b3dafa4ceb9461701143b78dba,

title = "Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells",

abstract = "Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterisation 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 (3 donors each) with adult mesenchymal fibroblasts using 8-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6000 proteins with high confidence. This approach identified 186 up-regulated proteins as mesenchymal progenitor biomarkers. Validation of 10 of these cell surface markers, including ROR2, EPHA2and PLXNA2, confirmed up-regulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration and differentiation. Thus cell surface protein enrichment plus isobaric-tag labelling prior to MS has delivered a comprehensive cell surface proteome repository that now enables improved selection and functional characterisation of human mesenchymal progenitor populations.",

author = "Holley, {Rebecca J.} and Guangping Tai and Williamson, {Andrew J. K.} and Samuel Taylor and Stuart Cain and Richardson, {Stephen M.} and Merry, {Catherine L. R.} and Whetton, {Anthony D.} and Canfield, {Ann E.}",

note = "This work was co-funded by the Medical Research Council and British Heart Foundation G0902170 (RJH, GT, CLRM, ADW, CMK, AEC). SAC is funded by a UK Regenerative Medicine Platform grant.",

year = "2015",

month = mar,

day = "10",

doi = "10.1016/j.stemcr.2015.01.007",

language = "English",

volume = "4",

pages = "473--488",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "3",

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TY - JOUR

T1 - Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells

AU - Holley, Rebecca J.

AU - Tai, Guangping

AU - Williamson, Andrew J. K.

AU - Taylor, Samuel

AU - Cain, Stuart

AU - Richardson, Stephen M.

AU - Merry, Catherine L. R.

AU - Whetton, Anthony D.

AU - Canfield, Ann E.

N1 - This work was co-funded by the Medical Research Council and British Heart Foundation G0902170 (RJH, GT, CLRM, ADW, CMK, AEC). SAC is funded by a UK Regenerative Medicine Platform grant.

PY - 2015/3/10

Y1 - 2015/3/10

N2 - Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterisation 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 (3 donors each) with adult mesenchymal fibroblasts using 8-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6000 proteins with high confidence. This approach identified 186 up-regulated proteins as mesenchymal progenitor biomarkers. Validation of 10 of these cell surface markers, including ROR2, EPHA2and PLXNA2, confirmed up-regulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration and differentiation. Thus cell surface protein enrichment plus isobaric-tag labelling prior to MS has delivered a comprehensive cell surface proteome repository that now enables improved selection and functional characterisation of human mesenchymal progenitor populations.

AB - Mesenchymal progenitor cells have great therapeutic potential, yet incomplete characterisation 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 (3 donors each) with adult mesenchymal fibroblasts using 8-channel isobaric-tagging mass spectrometry, yielding relative quantification on >6000 proteins with high confidence. This approach identified 186 up-regulated proteins as mesenchymal progenitor biomarkers. Validation of 10 of these cell surface markers, including ROR2, EPHA2and PLXNA2, confirmed up-regulated expression in mesenchymal progenitor populations and distinct roles in progenitor cell proliferation, migration and differentiation. Thus cell surface protein enrichment plus isobaric-tag labelling prior to MS has delivered a comprehensive cell surface proteome repository that now enables improved selection and functional characterisation of human mesenchymal progenitor populations.

U2 - 10.1016/j.stemcr.2015.01.007

DO - 10.1016/j.stemcr.2015.01.007

M3 - Article

C2 - 25684225

SN - 2213-6711

VL - 4

SP - 473

EP - 488

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

M1 - 25684225

ER -

Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells

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