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Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation
Skeletal aging is associated with reduced proliferative potential of bone marrow (BM) multipotential stromal cells (MSCs). Recent data suggest the involvement of type 1 interferon (IFN1) signalling in hematopoietic stem cell (HSC) senescence. Considering that BM-HSCs and BM-MSCs share the same BM ni...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399891/ https://www.ncbi.nlm.nih.gov/pubmed/32679782 http://dx.doi.org/10.3390/biomedicines8070214 |
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author | Ganguly, Payal Burska, Agata N. Davis, Charlotte L.M. El-Jawhari, Jehan J. Giannoudis, Peter V. Jones, Elena A. |
author_facet | Ganguly, Payal Burska, Agata N. Davis, Charlotte L.M. El-Jawhari, Jehan J. Giannoudis, Peter V. Jones, Elena A. |
author_sort | Ganguly, Payal |
collection | PubMed |
description | Skeletal aging is associated with reduced proliferative potential of bone marrow (BM) multipotential stromal cells (MSCs). Recent data suggest the involvement of type 1 interferon (IFN1) signalling in hematopoietic stem cell (HSC) senescence. Considering that BM-HSCs and BM-MSCs share the same BM niche, we investigated IFN1 expression profile in human BM-MSCs in relation to donor age, culture-expansion and IFN1 (α and β) stimulation. Fluorescence-activated cell sorting was used to purify uncultured BM-MSCs from younger (19–41, n = 6) and older (59–89, n = 6) donors based on the CD45(low)CD271(+) phenotype, and hematopoietic-lineage cells (BM-HLCs, CD45(+)CD271(−)) were used as controls. Gene expression was analysed using integrated circuits arrays in sorted fractions as well as cultured/stimulated BM-MSCs and Y201/Y202 immortalised cell lines. IFN1 stimulation led to BM-MSC growth arrest and upregulation of many IFN1-stimulated genes (ISGs), with IFNβ demonstrating stronger effects. Uncultured MSCs were characterised by a moderate-level ISG expression similar to Y201 cells. Age-related changes in ISG expression were negligible in BM-MSCs compared to BM-HLCs, and intracellular reactive oxygen species (ROS) levels in BM-MSCs did not significantly correlate with donor age. Antiaging genes Klotho and SIRT6 correlated with more ISGs in BM-MSCs than in BM-HLCs. In patients with osteoarthritis (OA), BM-MSCs expressed considerably lower levels of several ISGs, indicating that their IFN1 signature is affected in a pathological condition. In summary, BM-MSCs possess homeostatic IFN1 gene expression signature in health, which is sensitive to in vitro culture and external IFN1 stimulation. IFN signalling may facilitate in vivo BM-MSC responses to DNA damage and combating senescence and aberrant immune activation. |
format | Online Article Text |
id | pubmed-7399891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73998912020-08-17 Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation Ganguly, Payal Burska, Agata N. Davis, Charlotte L.M. El-Jawhari, Jehan J. Giannoudis, Peter V. Jones, Elena A. Biomedicines Article Skeletal aging is associated with reduced proliferative potential of bone marrow (BM) multipotential stromal cells (MSCs). Recent data suggest the involvement of type 1 interferon (IFN1) signalling in hematopoietic stem cell (HSC) senescence. Considering that BM-HSCs and BM-MSCs share the same BM niche, we investigated IFN1 expression profile in human BM-MSCs in relation to donor age, culture-expansion and IFN1 (α and β) stimulation. Fluorescence-activated cell sorting was used to purify uncultured BM-MSCs from younger (19–41, n = 6) and older (59–89, n = 6) donors based on the CD45(low)CD271(+) phenotype, and hematopoietic-lineage cells (BM-HLCs, CD45(+)CD271(−)) were used as controls. Gene expression was analysed using integrated circuits arrays in sorted fractions as well as cultured/stimulated BM-MSCs and Y201/Y202 immortalised cell lines. IFN1 stimulation led to BM-MSC growth arrest and upregulation of many IFN1-stimulated genes (ISGs), with IFNβ demonstrating stronger effects. Uncultured MSCs were characterised by a moderate-level ISG expression similar to Y201 cells. Age-related changes in ISG expression were negligible in BM-MSCs compared to BM-HLCs, and intracellular reactive oxygen species (ROS) levels in BM-MSCs did not significantly correlate with donor age. Antiaging genes Klotho and SIRT6 correlated with more ISGs in BM-MSCs than in BM-HLCs. In patients with osteoarthritis (OA), BM-MSCs expressed considerably lower levels of several ISGs, indicating that their IFN1 signature is affected in a pathological condition. In summary, BM-MSCs possess homeostatic IFN1 gene expression signature in health, which is sensitive to in vitro culture and external IFN1 stimulation. IFN signalling may facilitate in vivo BM-MSC responses to DNA damage and combating senescence and aberrant immune activation. MDPI 2020-07-15 /pmc/articles/PMC7399891/ /pubmed/32679782 http://dx.doi.org/10.3390/biomedicines8070214 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ganguly, Payal Burska, Agata N. Davis, Charlotte L.M. El-Jawhari, Jehan J. Giannoudis, Peter V. Jones, Elena A. Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title | Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title_full | Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title_fullStr | Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title_full_unstemmed | Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title_short | Intrinsic Type 1 Interferon (IFN1) Profile of Uncultured Human Bone Marrow CD45(low)CD271(+) Multipotential Stromal Cells (BM-MSCs): The Impact of Donor Age, Culture Expansion and IFNα and IFNβ Stimulation |
title_sort | intrinsic type 1 interferon (ifn1) profile of uncultured human bone marrow cd45(low)cd271(+) multipotential stromal cells (bm-mscs): the impact of donor age, culture expansion and ifnα and ifnβ stimulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399891/ https://www.ncbi.nlm.nih.gov/pubmed/32679782 http://dx.doi.org/10.3390/biomedicines8070214 |
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