title: The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse.
abstract: BACKGROUND
  The hematopoietic stem cells (HSCs) niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non-hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs).
  
  
  RESULTS
  Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE).
  
  
  CONCLUSIONS
  Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases.
authors.affiliation: Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA. Enrico.Pedemonte@ucsf.edu <Enrico.Pedemonte@ucsf.edu>
authors.forename: Enrico
authors.initials: E
authors.lastname: Pedemonte
authors.forename: Federica
authors.initials: F
authors.lastname: Benvenuto
authors.forename: Simona
authors.initials: S
authors.lastname: Casazza
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mancardi
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013569:Synapses; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D012333:RNA, Messenger