Direct Cardiac Epigenetic Reprogramming through Codelivery of 5′Azacytidine and miR-133a Nanoformulation
Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintain...
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| Vydáno v: | International Journal of Molecular Sciences Ročník 23; číslo 23; s. 15179 |
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| Jazyk: | angličtina |
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01.12.2022
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| ISSN: | 1422-0067, 1661-6596, 1422-0067 |
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| Abstract | Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular identities. For instance, DNA methylation controls cell differentiation in adults, establishing that epigenetic factors are crucial for sustaining altered gene expression patterns with subsequent rounds of cell division. This study attempts to demonstrate that 5′AZA and miR-133a encapsulated in PLGA-PEI nanocarriers induce direct epigenetic reprogramming of cardiac fibroblasts to cardiomyocyte-like cells. The results present a cardiomyocyte-like phenotype following seven days of the co-delivery of 5′AZA and miR-133a nanoformulation into human cardiac fibroblasts. Further evaluation of the global DNA methylation showed a decreased global 5-methylcytosine (5-medCyd) levels in the 5′AZA and 5′AZA/miR-133a treatment group compared to the untreated group and cells with void nanocarriers. These results suggest that the co-delivery of 5′AZA and miR-133a nanoformulation can induce the direct reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in-vitro, in addition to demonstrating the influence of miR-133a and 5′AZA as epigenetic regulators in dictating cell fate. |
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| AbstractList | Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular identities. For instance, DNA methylation controls cell differentiation in adults, establishing that epigenetic factors are crucial for sustaining altered gene expression patterns with subsequent rounds of cell division. This study attempts to demonstrate that 5′AZA and miR-133a encapsulated in PLGA-PEI nanocarriers induce direct epigenetic reprogramming of cardiac fibroblasts to cardiomyocyte-like cells. The results present a cardiomyocyte-like phenotype following seven days of the co-delivery of 5′AZA and miR-133a nanoformulation into human cardiac fibroblasts. Further evaluation of the global DNA methylation showed a decreased global 5-methylcytosine (5-medCyd) levels in the 5′AZA and 5′AZA/miR-133a treatment group compared to the untreated group and cells with void nanocarriers. These results suggest that the co-delivery of 5′AZA and miR-133a nanoformulation can induce the direct reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in-vitro, in addition to demonstrating the influence of miR-133a and 5′AZA as epigenetic regulators in dictating cell fate. |
| Audience | Academic |
| Author | Priyadharshni Muniyandi Tatsuro Hanajiri Toru Maekawa Vivekanandan Palaninathan |
| AuthorAffiliation | 1 Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe 3508585, Saitama, Japan 2 Bio-Nano Electronics Research Centre, Toyo University, 2100 Kujirai, Kawagoe 3508585, Saitama, Japan |
| AuthorAffiliation_xml | – name: 1 Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe 3508585, Saitama, Japan – name: 2 Bio-Nano Electronics Research Centre, Toyo University, 2100 Kujirai, Kawagoe 3508585, Saitama, Japan |
| Author_xml | – sequence: 1 givenname: Priyadharshni orcidid: 0000-0003-2028-842X surname: Muniyandi fullname: Muniyandi, Priyadharshni – sequence: 2 givenname: Vivekanandan orcidid: 0000-0003-1355-2720 surname: Palaninathan fullname: Palaninathan, Vivekanandan – sequence: 3 givenname: Tatsuro surname: Hanajiri fullname: Hanajiri, Tatsuro – sequence: 4 givenname: Toru surname: Maekawa fullname: Maekawa, Toru |
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| RelatedPersons | Singh, Vishwanath Pratap |
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| Snippet | Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of... |
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| StartPage | 15179 |
| SubjectTerms | Azacitidine Cardiomyocytes Cell differentiation Cellular Reprogramming DNA Methylation Efficiency Epigenetic inheritance Epigenetics Fibroblasts Gene expression Gene Expression Regulation Heart Humans Methylation MicroRNAs Morphology Myocytes, Cardiac Nanoparticles nanovectors; non-viral gene therapy; epigenetic reprogramming; direct reprogramming; 5′Azacytidine; MicroRNAs Polymers Polyvinyl alcohol Singh, Vishwanath Pratap Stem cells |
| Title | Direct Cardiac Epigenetic Reprogramming through Codelivery of 5′Azacytidine and miR-133a Nanoformulation |
| URI | https://cir.nii.ac.jp/crid/1870865118060946048 https://www.proquest.com/docview/2748552733 https://pubmed.ncbi.nlm.nih.gov/PMC9739153 |
| Volume | 23 |
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