{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327161/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Rattus norvegicus"],"gds_type":[" Genome binding/occupancy profiling by high throughput sequencing","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327161"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"YAP Promotes Microtubule Growth to Facilitate Sarcomere Disassembly in Adult Cardiomyocytes","description":"BACKGROUND: Mature mammalian cardiomyocytes (CMs) develop compact sarcomeric structures that inhibit proliferation. Consequently, CMs must dedifferentiate to a fetal-like state, which is accompanied by sarcomere disassembly, to enable successful cytokinesis. However, the regulation and coordination of CM dedifferentiation, cell cycle progression, and sarcomere reorganization remain unclear. METHODS: We generated adenovirus and adeno-associated virus (MyoAAV) vectors expressing YAP5SA and YAP5SA-S94A under Xon control for LMI070-inducible protein expression. We also developed MyoAAV-cTnT-Tuba1b-shRNA-miR30 for cardiomyocyte-specific knockdown (KD) of Tuba1b. These tools were used to investigated cardiomyocyte dedifferentiation, proliferation, and sarcomere disassembly. We also performed Cleavage Under Targets and Release Using Nuclease (CUT&RUN) to map the genome-wide binding sites of YAP5SA and YAP5SA-S94A, in combination with RNA sequencing to identify YAP target genes. In addition, time-course live-imaging analysis was used to evaluate microtubule and sarcomere dynamics in adult cardiomyocytes. RESULTS: We show that microtubule expression and network density decline with cardiac maturation. Overexpression of YAP5SA, a constitutively active YAP mutant, promotes microtubule growth by stabilizing the microtubule dynamics, leading to CM dedifferentiation, cell cycle re-entry and sarcomere disassembly. In contrast, colchicine blocks these processes and significantly attenuates YAP-induced cardiac regeneration. Live imaging reveals a distinct mode of sarcomere disassembly driven by enhanced microtubule polymerization, where microtubule plus-ends directly interact with α-actinin and displace α-actinin fragments, thereby facilitating sarcomere breakdown. Furthermore, the YAP-S94A mutation, which disrupts the YAP and TEAD interaction, significantly reduces YAP5SA-induced microtubule growth, sarcomere disassembly, and cell cycle activity. Mechanistically, CUT&RUN combined with RNA-seq identified direct YAP targets, including Ajuba and Tuba1b, which are critical for microtubule growth. CM-specific KD of Tuba1b attenuates YAP-driven sarcomere disassembly. CONCLUSIONS: These findings identify microtubule networks as an essential regulator modulating CM dedifferentiation and sarcomere reorganization, which is critical for CM cytokinesis and cardiac regenerative repair.","dates":{"publication":"2026/07/01"},"accession":"GSE327161","cross_references":{"GSM":["GSM9650161","GSM9650160","GSM9650165","GSM9650164","GSM9650163","GSM9650162","GSM9650168","GSM9650167","GSM9650166","GSM9650159"],"GPL":["34316"],"GSE":["327161"],"taxon":["Rattus norvegicus"]}}