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Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes
BACKGROUND: Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are widely used models for regenerative medicine and disease research. However, PSC-CMs are usually immature in morphology and functionality and the maturity of PSC-CMs could not be determined accurately. In order to reasonably inter...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440140/ https://www.ncbi.nlm.nih.gov/pubmed/30925936 http://dx.doi.org/10.1186/s13287-019-1205-1 |
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author | Chen, Rou He, Jun Wang, Yumei Guo, You Zhang, Juan Peng, Luying Wang, Duo Lin, Qin Zhang, Jie Guo, Zheng Li, Li |
author_facet | Chen, Rou He, Jun Wang, Yumei Guo, You Zhang, Juan Peng, Luying Wang, Duo Lin, Qin Zhang, Jie Guo, Zheng Li, Li |
author_sort | Chen, Rou |
collection | PubMed |
description | BACKGROUND: Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are widely used models for regenerative medicine and disease research. However, PSC-CMs are usually immature in morphology and functionality and the maturity of PSC-CMs could not be determined accurately. In order to reasonably interpret the experimental results obtained by PSC-CMs, it is necessary to evaluate the maturity of PSC-CMs and find the key genes related to maturation. METHODS: Using the gene expression profiles of normal adult cardiac tissue and embryonic stem cell (ESC) samples, we identified gene pairs with identically relative expression orderings (REOs) within adult cardiac tissue but reversely identical in ESCs. Then, for a PSC-CM model, we calculated the maturity score as the percentage of these gene pairs that exhibit the same REOs in adult cardiac tissue. Lastly, the CellComp method was used to identify the maturation-related genes. RESULTS: The maturity score increased gradually from 0.8401 for 18-week fetal cardiac tissue to 0.9997 for adult cardiac tissue. For four human PSC-CM models, the mature scores increased with prolonged culture time but were all below 0.8. The genes involved in energy metabolism, angiogenesis, immunity, and proliferation were dysregulated in the 1-year PSC-CMs compared with adult cardiac tissue. CONCLUSION: We proposed a qualitative transcriptional signature to score the maturity degree of PSC-CMs. This score can reasonably track the maturity of PSC-CMs and be used to compare different PSC-CM culture methods. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1205-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6440140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64401402019-04-11 Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes Chen, Rou He, Jun Wang, Yumei Guo, You Zhang, Juan Peng, Luying Wang, Duo Lin, Qin Zhang, Jie Guo, Zheng Li, Li Stem Cell Res Ther Research BACKGROUND: Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are widely used models for regenerative medicine and disease research. However, PSC-CMs are usually immature in morphology and functionality and the maturity of PSC-CMs could not be determined accurately. In order to reasonably interpret the experimental results obtained by PSC-CMs, it is necessary to evaluate the maturity of PSC-CMs and find the key genes related to maturation. METHODS: Using the gene expression profiles of normal adult cardiac tissue and embryonic stem cell (ESC) samples, we identified gene pairs with identically relative expression orderings (REOs) within adult cardiac tissue but reversely identical in ESCs. Then, for a PSC-CM model, we calculated the maturity score as the percentage of these gene pairs that exhibit the same REOs in adult cardiac tissue. Lastly, the CellComp method was used to identify the maturation-related genes. RESULTS: The maturity score increased gradually from 0.8401 for 18-week fetal cardiac tissue to 0.9997 for adult cardiac tissue. For four human PSC-CM models, the mature scores increased with prolonged culture time but were all below 0.8. The genes involved in energy metabolism, angiogenesis, immunity, and proliferation were dysregulated in the 1-year PSC-CMs compared with adult cardiac tissue. CONCLUSION: We proposed a qualitative transcriptional signature to score the maturity degree of PSC-CMs. This score can reasonably track the maturity of PSC-CMs and be used to compare different PSC-CM culture methods. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1205-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-29 /pmc/articles/PMC6440140/ /pubmed/30925936 http://dx.doi.org/10.1186/s13287-019-1205-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Chen, Rou He, Jun Wang, Yumei Guo, You Zhang, Juan Peng, Luying Wang, Duo Lin, Qin Zhang, Jie Guo, Zheng Li, Li Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title | Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title_full | Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title_fullStr | Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title_full_unstemmed | Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title_short | Qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
title_sort | qualitative transcriptional signatures for evaluating the maturity degree of pluripotent stem cell-derived cardiomyocytes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440140/ https://www.ncbi.nlm.nih.gov/pubmed/30925936 http://dx.doi.org/10.1186/s13287-019-1205-1 |
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