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2016 ; 4
(ä): e1845
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A molecular classification of human mesenchymal stromal cells
#MMPMID27042394
Rohart F
; Mason EA
; Matigian N
; Mosbergen R
; Korn O
; Chen T
; Butcher S
; Patel J
; Atkinson K
; Khosrotehrani K
; Fisk NM
; Lê Cao KA
; Wells CA
PeerJ
2016[]; 4
(ä): e1845
PMID27042394
show ga
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.
free
free
free
