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HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA

Multipotent human mesenchymal stem cells (MSCs) harbor clinically relevant immunomodulation, and HLA-G, a non-classical MHC class I molecule with highly restricted tissue expression, is one important molecule involved in these processes. Understanding of the natural regulatory mechanisms involved in...

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Autores principales: Yen, B. Linju, Hwa, Hsiao-Lin, Hsu, Pei-Ju, Chen, Pei-Min, Wang, Li-Tzu, Jiang, Shih-Sheng, Liu, Ko-Jiunn, Sytwu, Huey-Kang, Yen, Men-Luh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404323/
https://www.ncbi.nlm.nih.gov/pubmed/32708387
http://dx.doi.org/10.3390/ijms21145075
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author Yen, B. Linju
Hwa, Hsiao-Lin
Hsu, Pei-Ju
Chen, Pei-Min
Wang, Li-Tzu
Jiang, Shih-Sheng
Liu, Ko-Jiunn
Sytwu, Huey-Kang
Yen, Men-Luh
author_facet Yen, B. Linju
Hwa, Hsiao-Lin
Hsu, Pei-Ju
Chen, Pei-Min
Wang, Li-Tzu
Jiang, Shih-Sheng
Liu, Ko-Jiunn
Sytwu, Huey-Kang
Yen, Men-Luh
author_sort Yen, B. Linju
collection PubMed
description Multipotent human mesenchymal stem cells (MSCs) harbor clinically relevant immunomodulation, and HLA-G, a non-classical MHC class I molecule with highly restricted tissue expression, is one important molecule involved in these processes. Understanding of the natural regulatory mechanisms involved in expression of this elusive molecule has been difficult, with near exclusive reliance on cancer cell lines. We therefore studied the transcriptional control of HLA-G in primary isolated human bone marrow- (BM), human embryonic stem cell-derived (hE-), as well as placenta-derived MSCs (P-MSCs), and found that all 3 types of MSCs express 3 of the 7 HLA-G isoforms at the gene level; however, fibroblasts did not express HLA-G. Protein validation using BM- and P-MSCs demonstrated expression of 2 isoforms including a larger HLA-G-like protein. Interferon-γ (IFN-γ) stimulation upregulated both gene and protein expression in MSCs but not the constitutively expressing JEG-3 cell line. Most interestingly in human MSCs and placental tissue, hypomethylation of CpG islands not only occurs on the HLA-G proximal promoter but also on the gene body as well, a pattern not seen in either of the 2 commonly used choriocarcinoma cell lines which may contribute to the unique HLA-G expression patterns and IFN-γ-responsiveness in MSCs. Our study implicates the importance of using normal cells and tissues for physiologic understanding of tissue-specific transcriptional regulation, and highlight the utility of human MSCs in unraveling the transcriptional regulation of HLA-G for better therapeutic application.
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spelling pubmed-74043232020-08-18 HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA Yen, B. Linju Hwa, Hsiao-Lin Hsu, Pei-Ju Chen, Pei-Min Wang, Li-Tzu Jiang, Shih-Sheng Liu, Ko-Jiunn Sytwu, Huey-Kang Yen, Men-Luh Int J Mol Sci Article Multipotent human mesenchymal stem cells (MSCs) harbor clinically relevant immunomodulation, and HLA-G, a non-classical MHC class I molecule with highly restricted tissue expression, is one important molecule involved in these processes. Understanding of the natural regulatory mechanisms involved in expression of this elusive molecule has been difficult, with near exclusive reliance on cancer cell lines. We therefore studied the transcriptional control of HLA-G in primary isolated human bone marrow- (BM), human embryonic stem cell-derived (hE-), as well as placenta-derived MSCs (P-MSCs), and found that all 3 types of MSCs express 3 of the 7 HLA-G isoforms at the gene level; however, fibroblasts did not express HLA-G. Protein validation using BM- and P-MSCs demonstrated expression of 2 isoforms including a larger HLA-G-like protein. Interferon-γ (IFN-γ) stimulation upregulated both gene and protein expression in MSCs but not the constitutively expressing JEG-3 cell line. Most interestingly in human MSCs and placental tissue, hypomethylation of CpG islands not only occurs on the HLA-G proximal promoter but also on the gene body as well, a pattern not seen in either of the 2 commonly used choriocarcinoma cell lines which may contribute to the unique HLA-G expression patterns and IFN-γ-responsiveness in MSCs. Our study implicates the importance of using normal cells and tissues for physiologic understanding of tissue-specific transcriptional regulation, and highlight the utility of human MSCs in unraveling the transcriptional regulation of HLA-G for better therapeutic application. MDPI 2020-07-18 /pmc/articles/PMC7404323/ /pubmed/32708387 http://dx.doi.org/10.3390/ijms21145075 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
Yen, B. Linju
Hwa, Hsiao-Lin
Hsu, Pei-Ju
Chen, Pei-Min
Wang, Li-Tzu
Jiang, Shih-Sheng
Liu, Ko-Jiunn
Sytwu, Huey-Kang
Yen, Men-Luh
HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title_full HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title_fullStr HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title_full_unstemmed HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title_short HLA-G Expression in Human Mesenchymal Stem Cells (MSCs) Is Related to Unique Methylation Pattern in the Proximal Promoter as well as Gene Body DNA
title_sort hla-g expression in human mesenchymal stem cells (mscs) is related to unique methylation pattern in the proximal promoter as well as gene body dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404323/
https://www.ncbi.nlm.nih.gov/pubmed/32708387
http://dx.doi.org/10.3390/ijms21145075
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