The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse

<p>Abstract</p> <p>Background</p> <p>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...

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Main Authors: Mancardi Gianluigi, Casazza Simona, Benvenuto Federica, Pedemonte Enrico, Oksenberg Jorge R, Uccelli Antonio, Baranzini Sergio E
Format: Article
Language:English
Published: BMC 2007-03-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/8/65
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author Mancardi Gianluigi
Casazza Simona
Benvenuto Federica
Pedemonte Enrico
Oksenberg Jorge R
Uccelli Antonio
Baranzini Sergio E
author_facet Mancardi Gianluigi
Casazza Simona
Benvenuto Federica
Pedemonte Enrico
Oksenberg Jorge R
Uccelli Antonio
Baranzini Sergio E
author_sort Mancardi Gianluigi
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-7e4d8e1a14c74889b62aef3caf9115a32022-12-22T01:25:06ZengBMCBMC Genomics1471-21642007-03-01816510.1186/1471-2164-8-65The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapseMancardi GianluigiCasazza SimonaBenvenuto FedericaPedemonte EnricoOksenberg Jorge RUccelli AntonioBaranzini Sergio E<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/8/65
spellingShingle Mancardi Gianluigi
Casazza Simona
Benvenuto Federica
Pedemonte Enrico
Oksenberg Jorge R
Uccelli Antonio
Baranzini Sergio E
The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
BMC Genomics
title The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
title_full The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
title_fullStr The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
title_full_unstemmed The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
title_short The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
title_sort molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse
url http://www.biomedcentral.com/1471-2164/8/65
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