https://tulab.genetics.ac.cn/author/ye-bu/ Ye Bu Hugo Blox Builder (https://hugoblox.com)en-usThu, 07 Apr 2022 00:00:00 +0000 https://tulab.genetics.ac.cn/media/icon_hu_c372438749b9f15a.png https://tulab.genetics.ac.cn/author/ye-bu/ https://tulab.genetics.ac.cn/publications/2022-cellstemcell/ Thu, 07 Apr 2022 00:00:00 +0000 https://tulab.genetics.ac.cn/publications/2022-cellstemcell/ <!-- <div class="alert alert-note"> <div> Click the <em>Cite</em> button above to demo the feature to enable visitors to import publication metadata into their reference management software. </div> </div> <div class="alert alert-note"> <div> Create your slides in Markdown - click the <em>Slides</em> button to check out the example. </div> </div> Add the publication's **full text** or **supplementary notes** here. You can use rich formatting such as including [code, math, and images](https://docs.hugoblox.com/content/writing-markdown-latex/). --> <p>Abstract: Zebrafish and mammalian neonates possess robust cardiac regeneration via the induction of endogenous cardiomyocyte (CM) proliferation, but adult mammalian hearts have very limited regenerative potential. Developing small molecules for inducing adult mammalian heart regeneration has had limited success. We report a chemical cocktail of five small molecules (5SM) that promote adult CM proliferation and heart regeneration. A high-content chemical screen, along with an algorithm-aided prediction of small-molecule interactions, identified 5SM that efficiently induced CM cell cycle re-entry and cytokinesis. Intraperitoneal delivery of 5SM reversed the loss of heart function, induced CM proliferation, and decreased cardiac fibrosis after rat myocardial infarction. Mechanistically, 5SM potentially targets α1 adrenergic receptor, JAK1, DYRKs, PTEN, and MCT1 and is connected to lactate-LacRS2 signaling, leading to CM metabolic switching toward glycolysis/biosynthesis and CM de-differentiation before entering the cell-cycle. Our work sheds lights on the understanding CM regenerative mechanisms and opens therapeutic avenues for repairing the heart.</p>