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Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta
BACKGROUND: Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287589/ https://www.ncbi.nlm.nih.gov/pubmed/25326687 http://dx.doi.org/10.1186/1471-2164-15-910 |
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author | Roson-Burgo, Beatriz Sanchez-Guijo, Fermin Del Cañizo, Consuelo De Las Rivas, Javier |
author_facet | Roson-Burgo, Beatriz Sanchez-Guijo, Fermin Del Cañizo, Consuelo De Las Rivas, Javier |
author_sort | Roson-Burgo, Beatriz |
collection | PubMed |
description | BACKGROUND: Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many questions about their molecular identity remain uncertain. RESULTS: MSC primary cultures from human bone marrow (BM) and placenta (PL) were derived and verified by their immunophenotype standard pattern and trilineage differentiation potential. Then, a broad characterization of the transcriptome of these MSCs was performed using RNA deep sequencing (RNA-Seq). Quantitative analysis of these data rendered an extensive expression footprint that includes 5,271 protein-coding genes. Flow cytometry assays of canonical MSC CD-markers were congruent with their expression levels detected by the RNA-Seq. Expression of other recently proposed MSC markers (CD146, Nestin and CD271) was tested in the placenta samples, finding only CD146 and Nestin. Functional analysis revealed enrichment in stem cell related genes and mesenchymal regulatory transcription factors (TFs). Analysis of TF binding sites (TFBSs) identified 11 meta-regulators, including factors KLF4 and MYC among them. Epigenetically, hypomethylated promoter patterns supported the active expression of the MSC TFs found. An interaction network of these TFs was built to show up their links and relations. Assessment of dissimilarities between cell origins (BM versus PL) disclosed two hundred differentially expressed genes enrolled in microenvironment processes related to the cellular niche, as regulation of bone formation and blood vessel morphogenesis for the case of BM-MSCs. By contrast genes overexpressed in PL-MSCs showed functional enrichment on mitosis, negative regulation of cell-death and embryonic morphogenesis that supported the higher growth rates observed in the cultures of these fetal cells and their closer links with development processes. CONCLUSIONS: The results present a transcriptomic portrait of the human MSCs isolated from bone marrow and placenta. The data are released as a cell-specific resource, providing a comprehensive expression footprint of the MSCs useful to better understand their cellular and molecular biology and for further investigations on the isolation and biomedical use of these multipotent cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-910) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4287589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42875892015-01-10 Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta Roson-Burgo, Beatriz Sanchez-Guijo, Fermin Del Cañizo, Consuelo De Las Rivas, Javier BMC Genomics Research Article BACKGROUND: Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many questions about their molecular identity remain uncertain. RESULTS: MSC primary cultures from human bone marrow (BM) and placenta (PL) were derived and verified by their immunophenotype standard pattern and trilineage differentiation potential. Then, a broad characterization of the transcriptome of these MSCs was performed using RNA deep sequencing (RNA-Seq). Quantitative analysis of these data rendered an extensive expression footprint that includes 5,271 protein-coding genes. Flow cytometry assays of canonical MSC CD-markers were congruent with their expression levels detected by the RNA-Seq. Expression of other recently proposed MSC markers (CD146, Nestin and CD271) was tested in the placenta samples, finding only CD146 and Nestin. Functional analysis revealed enrichment in stem cell related genes and mesenchymal regulatory transcription factors (TFs). Analysis of TF binding sites (TFBSs) identified 11 meta-regulators, including factors KLF4 and MYC among them. Epigenetically, hypomethylated promoter patterns supported the active expression of the MSC TFs found. An interaction network of these TFs was built to show up their links and relations. Assessment of dissimilarities between cell origins (BM versus PL) disclosed two hundred differentially expressed genes enrolled in microenvironment processes related to the cellular niche, as regulation of bone formation and blood vessel morphogenesis for the case of BM-MSCs. By contrast genes overexpressed in PL-MSCs showed functional enrichment on mitosis, negative regulation of cell-death and embryonic morphogenesis that supported the higher growth rates observed in the cultures of these fetal cells and their closer links with development processes. CONCLUSIONS: The results present a transcriptomic portrait of the human MSCs isolated from bone marrow and placenta. The data are released as a cell-specific resource, providing a comprehensive expression footprint of the MSCs useful to better understand their cellular and molecular biology and for further investigations on the isolation and biomedical use of these multipotent cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-910) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-19 /pmc/articles/PMC4287589/ /pubmed/25326687 http://dx.doi.org/10.1186/1471-2164-15-910 Text en © Roson-Burgo et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Roson-Burgo, Beatriz Sanchez-Guijo, Fermin Del Cañizo, Consuelo De Las Rivas, Javier Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title | Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title_full | Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title_fullStr | Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title_full_unstemmed | Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title_short | Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta |
title_sort | transcriptomic portrait of human mesenchymal stromal/stem cells isolated from bone marrow and placenta |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287589/ https://www.ncbi.nlm.nih.gov/pubmed/25326687 http://dx.doi.org/10.1186/1471-2164-15-910 |
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