The role of c-Jun for beating cardiomycyte formation in prepared embryonic body
Abstract Background Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03544-9 |
| _version_ | 1797377160360493056 |
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| author | Lide Su Guofu Zhang Lili Jiang Chao Chi Bing Bai Kai Kang |
| author_facet | Lide Su Guofu Zhang Lili Jiang Chao Chi Bing Bai Kai Kang |
| author_sort | Lide Su |
| collection | DOAJ |
| description | Abstract Background Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation. Methods The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses. Results Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group. Conclusions Knocking out c-Jun directs ESCs toward a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development. |
| first_indexed | 2024-03-08T19:49:41Z |
| format | Article |
| id | doaj.art-caa4c35feb004444b99753dbb7a788c0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-08T19:49:41Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-caa4c35feb004444b99753dbb7a788c02023-12-24T12:11:14ZengBMCStem Cell Research & Therapy1757-65122023-12-011411910.1186/s13287-023-03544-9The role of c-Jun for beating cardiomycyte formation in prepared embryonic bodyLide Su0Guofu Zhang1Lili Jiang2Chao Chi3Bing Bai4Kai Kang5Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Pediatric Dentistry, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical UniversityAbstract Background Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation. Methods The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses. Results Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group. Conclusions Knocking out c-Jun directs ESCs toward a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.https://doi.org/10.1186/s13287-023-03544-9C-JunCardiac differentiationMesodermEndodermEmbryonic body |
| spellingShingle | Lide Su Guofu Zhang Lili Jiang Chao Chi Bing Bai Kai Kang The role of c-Jun for beating cardiomycyte formation in prepared embryonic body Stem Cell Research & Therapy C-Jun Cardiac differentiation Mesoderm Endoderm Embryonic body |
| title | The role of c-Jun for beating cardiomycyte formation in prepared embryonic body |
| title_full | The role of c-Jun for beating cardiomycyte formation in prepared embryonic body |
| title_fullStr | The role of c-Jun for beating cardiomycyte formation in prepared embryonic body |
| title_full_unstemmed | The role of c-Jun for beating cardiomycyte formation in prepared embryonic body |
| title_short | The role of c-Jun for beating cardiomycyte formation in prepared embryonic body |
| title_sort | role of c jun for beating cardiomycyte formation in prepared embryonic body |
| topic | C-Jun Cardiac differentiation Mesoderm Endoderm Embryonic body |
| url | https://doi.org/10.1186/s13287-023-03544-9 |
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