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The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome

MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcrip...

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Autores principales: Arasaratnam, Deevina, Bell, Katrina M., Sim, Choon Boon, Koutsis, Kathy, Anderson, David J., Qian, Elizabeth L., Stanley, Edouard G., Elefanty, Andrew G., Cheung, Michael M., Oshlack, Alicia, White, Anthony J., Abi Khalil, Charbel, Hudson, James E., Porrello, Enzo R., Elliott, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828809/
https://www.ncbi.nlm.nih.gov/pubmed/31685864
http://dx.doi.org/10.1038/s41598-019-52280-9
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author Arasaratnam, Deevina
Bell, Katrina M.
Sim, Choon Boon
Koutsis, Kathy
Anderson, David J.
Qian, Elizabeth L.
Stanley, Edouard G.
Elefanty, Andrew G.
Cheung, Michael M.
Oshlack, Alicia
White, Anthony J.
Abi Khalil, Charbel
Hudson, James E.
Porrello, Enzo R.
Elliott, David A.
author_facet Arasaratnam, Deevina
Bell, Katrina M.
Sim, Choon Boon
Koutsis, Kathy
Anderson, David J.
Qian, Elizabeth L.
Stanley, Edouard G.
Elefanty, Andrew G.
Cheung, Michael M.
Oshlack, Alicia
White, Anthony J.
Abi Khalil, Charbel
Hudson, James E.
Porrello, Enzo R.
Elliott, David A.
author_sort Arasaratnam, Deevina
collection PubMed
description MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcription factors such as NKX2-5 regulate miRNA expression. We used an NKX2-5(eGFP/w) reporter line to isolate both cardiac committed mesoderm and cardiomyocytes. We identified 11 miRNAs that were differentially expressed in NKX2-5 -expressing cardiac mesoderm compared to non-cardiac mesoderm. Subsequent profiling revealed that the canonical myogenic miRNAs including MIR1-1, MIR133A1 and MIR208A were enriched in cardiomyocytes. Strikingly, deletion of NKX2-5 did not result in gross changes in the cardiac miRNA profile, either at committed mesoderm or cardiomyocyte stages. Thus, in early human cardiomyocyte commitment and differentiation, the cardiac myogenic miRNA program is predominantly regulated independently of the highly conserved NKX2-5 -dependant gene regulatory network.
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spelling pubmed-68288092019-11-12 The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome Arasaratnam, Deevina Bell, Katrina M. Sim, Choon Boon Koutsis, Kathy Anderson, David J. Qian, Elizabeth L. Stanley, Edouard G. Elefanty, Andrew G. Cheung, Michael M. Oshlack, Alicia White, Anthony J. Abi Khalil, Charbel Hudson, James E. Porrello, Enzo R. Elliott, David A. Sci Rep Article MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcription factors such as NKX2-5 regulate miRNA expression. We used an NKX2-5(eGFP/w) reporter line to isolate both cardiac committed mesoderm and cardiomyocytes. We identified 11 miRNAs that were differentially expressed in NKX2-5 -expressing cardiac mesoderm compared to non-cardiac mesoderm. Subsequent profiling revealed that the canonical myogenic miRNAs including MIR1-1, MIR133A1 and MIR208A were enriched in cardiomyocytes. Strikingly, deletion of NKX2-5 did not result in gross changes in the cardiac miRNA profile, either at committed mesoderm or cardiomyocyte stages. Thus, in early human cardiomyocyte commitment and differentiation, the cardiac myogenic miRNA program is predominantly regulated independently of the highly conserved NKX2-5 -dependant gene regulatory network. Nature Publishing Group UK 2019-11-04 /pmc/articles/PMC6828809/ /pubmed/31685864 http://dx.doi.org/10.1038/s41598-019-52280-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Arasaratnam, Deevina
Bell, Katrina M.
Sim, Choon Boon
Koutsis, Kathy
Anderson, David J.
Qian, Elizabeth L.
Stanley, Edouard G.
Elefanty, Andrew G.
Cheung, Michael M.
Oshlack, Alicia
White, Anthony J.
Abi Khalil, Charbel
Hudson, James E.
Porrello, Enzo R.
Elliott, David A.
The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title_full The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title_fullStr The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title_full_unstemmed The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title_short The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome
title_sort role of cardiac transcription factor nkx2-5 in regulating the human cardiac mirnaome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828809/
https://www.ncbi.nlm.nih.gov/pubmed/31685864
http://dx.doi.org/10.1038/s41598-019-52280-9
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