Rachel Forman-Rubinsky, Angela Paul, Wei Feng, Brent T Schlegel, Daniel A Zuppo, Katarzyna Kedziora, Donna B Stoltz, Simon C Watkins, Dhivyaa Rajasundaram, Guang Li, Michael Tsang
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引用次数: 0
Abstract
Cardiac regeneration involves the interplay of complex interactions between many different cell types, including cardiomyocytes. In regeneration, cardiomyocytes undergo dedifferentiation and proliferation to replace lost cells at the injury border. The exact mechanism regulating this process is not completely understood. Here, we report a single nucleus RNA-sequencing profile of the injured zebrafish heart revealing distinct cardiomyocyte populations. These cardiomyocyte populations have diverse functions, including stress response, myofibril assembly, proliferation and contraction. Notably, increased expression of cited4a, a p300/CBP transcriptional coactivator, was detected in the mature contracting cardiomyocytes, but absent from proliferating cardiomyocytes, suggesting it may play a role in maintaining contractile function in a subset of cardiomyocytes. We reasoned that cited4a is induced in heart injury to maintain cardiomyocyte function and therefore cited4a+ populations are restricted from entering the cell cycle. Loss-of-function cited4a mutants were generated and, following ventricular resection, increased cardiomyocyte dedifferentiation and proliferation was observed. Our findings indicate that suppressing cited4a activity in the injured heart expands the pool of cardiomyocytes available for replacing damaged and lost myocardium and could be an approach to promote heart regeneration.
期刊介绍：
Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication.
To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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