title: A molecular classification of human mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonly used to describe and compare different cell types; however, efforts to identify specific markers of rare cellular subsets may be confounded by the small sample sizes of most studies. Consequently, it is difficult to derive reproducible, and therefore useful markers. We addressed the question of MSC classification with a large integrative analysis of many public MSC datasets. We derived a sparse classifier (The Rohart MSC test) that accurately distinguished MSC from non-MSC samples with >97% accuracy on an internal training set of 635 samples from 41 studies derived on 10 different microarray platforms. The classifier was validated on an external test set of 1,291 samples from 65 studies derived on 15 different platforms, with >95% accuracy. The genes that contribute to the MSC classifier formed a protein-interaction network that included known MSC markers. Further evidence of the relevance of this new MSC panel came from the high number of Mendelian disorders associated with mutations in more than 65% of the network. These result in mesenchymal defects, particularly impacting on skeletal growth and function. The Rohart MSC test is a simple in silico test that accurately discriminates MSC from fibroblasts, other adult stem/progenitor cell types or differentiated stromal cells. It has been implemented in the www.stemformatics.org resource, to assist researchers wishing to benchmark their own MSC datasets or data from the public domain. The code is available from the CRAN repository and all data used to generate the MSC test is available to download via the Gene Expression Omnibus or the Stemformatics resource.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; The University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Rohart
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland , Brisbane, Queensland , Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mason
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; The University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Matigian
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; Department of Anatomy and Neuroscience, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Rowland
authors.initials: R
authors.lastname: Mosbergen
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland , Brisbane, Queensland , Australia.
authors.forename: Othmar
authors.initials: O
authors.lastname: Korn
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; Department of Anatomy and Neuroscience, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Tyrone
authors.initials: T
authors.lastname: Chen
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; Department of Anatomy and Neuroscience, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Butcher
authors.affiliation: The University of Queensland Centre for Clinical Research, University of Queensland , Brisbane, Queensland , Australia.
authors.forename: Jatin
authors.initials: J
authors.lastname: Patel
authors.affiliation: The University of Queensland Centre for Clinical Research, University of Queensland , Brisbane, Queensland , Australia.
authors.forename: Kerry
authors.initials: K
authors.lastname: Atkinson
authors.affiliation: The University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia; Centre for Advanced Prenatal Care, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
authors.affiliation: The University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia; Centre for Advanced Prenatal Care, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland , Brisbane, Queensland , Australia.
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Lê Cao
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia; Department of Anatomy and Neuroscience, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wells
keywords: Data integration; Mesenchymal stromal cells; Meta-analysis; Sparse classification; Stem cell classification; Transcriptome