Gene expression profile of human cardiac fibroblasts (HCFs), induced cardiomyocytes (iCMs), and heart
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56874 | GEO | 2014/07/03
SECONDARY ACCESSION(S): PRJNA244923
REPOSITORIES: GEO
Similar Datasets
Project description:Global gene expression profile of total 24460 probes in the iCMs. The gene expression shifts from a fibroblast state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5/Mesp1/Myocd (GMTMM) or GMTMM/miR-133 transduction at 7 days after transduction. MiR-133 silenced fibroblast signatures in parallel with cardiac gene activation, and Snai1 overexpression inhibited the effects of miR-133-mediated cardiac reprogramming. HCFs were used for negative control, human heart tissue for positive control. Gene expression profiles were compared among HCFs, iCMs and heart. 24460 probes were analyzed in each experiment.
2014-07-03 | E-GEOD-56874 | biostudies-arrayexpress
Project description:Global gene expression patterns of the iCMs shift from a MEF state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5 (GMT) or GMT/miR-133 transduction at 3, 7 and 18 days after transduction (D3, D7 and D18) MiR-133 silenced fibroblast signatures in parallel with cardiac gene activation, and Snai1 overexpression inhibited the effects of miR-133-mediated cardiac reprogramming.
2014-07-03 | GSE56875 | GEO
Project description:Global gene expression patterns of the iCMs shift from a MEF state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5 (GMT) or GMT/miR-133 transduction at 3, 7 and 18 days after transduction (D3, D7 and D18) MiR-133 silenced fibroblast signatures in parallel with cardiac gene activation, and Snai1 overexpression inhibited the effects of miR-133-mediated cardiac reprogramming. MEFs were used for negative control, mouse heart tissue for positive control. Gene expression profiles were compared among MEFs, iCMs and heart. 23474 probes were analyzed in each experiment.
2014-07-03 | E-GEOD-56875 | biostudies-arrayexpress
Project description:Global gene expression patterns of the iCMs shift from a MEF state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5 (GMT) or GMT/Hand2 (GHMT) transduction at 2 and 4 weeks after transduction (2W, 4W). Hand2 upregulated a panel of cardiac genes and suppressed cell cylce genes during cardiac reprogramming.
2017-09-26 | GSE101578 | GEO
Project description:We report that Sall4 and Myocd empower direct cardiac reprogramming from adult cardiac fibroblasts after myocardial infarction (MICFs). To examine the gene expression of induced cardiomyocytes (iCMs) on the genome-wide scale, we performed RNA-sequencing of MICFs and iCMs induced by GMTMS (our cocktails) or GMTMM (cocktails reported by Weda et al). We found significant changes in the global gene expression profiles of MICFs after GMTMS or GMTMM overexpression. Compared to MICFs, 1318 genes were significantly up-regulated and 1302 genes were significantly down-regulated in GMTMS-induced iCMs, in which high expression of many cardiac genes and concomitant suppression of fibroblast genes were observed. Go analysis revealed that many cardiac-related clusters were enriched in iCMs as well. These results demonstrate a cardiac-like phenotype reprogrammed from MICFs by GMTMS.
2021-02-25 | GSE167436 | GEO
Project description:Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). Results: To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human iCMs and functional cardiomyocytes (CMs). We identified T-box transcription factor TBX20 as the top CM gene that is unable to be activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significantly activated contractility gene programs and signatures more similar to ventricular CMs. Human iCMs produced with MGT133+TBX20 more frequently demonstrated beating and calcium oscillation in co-culture with pluripotent stem cell derived CMs. More mitochondria and higher mitochondrial respiration were also detected in iCMs after TBX20 overexpression. Mechanistically, comprehensive transcriptomic, chromatin occupancy and epigenomic integration revealed that TBX20 localized to the cis-regulatory enhancers of under-expressed cardiac genes, such as MYBPC3, MYH7 and MYL4, to activate gene expression via strengthening the occupancy and co-occupancy of transcription factors. Furthermore, we identified TBX20-regulated enhancers and confirmed the synergistic effect of MGT and TBX20 on enhancer activation. Conclusions: TBX20 promotes cardiac cell fate conversion via direct activating cardiac enhancers. Human iCMs generated with TBX20 showed enhanced cardiac function in terms of contractility and mitochondrial respiration.
2022-09-14 | GSE193789 | GEO
Project description:Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). Results: To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human iCMs and functional cardiomyocytes (CMs). We identified T-box transcription factor TBX20 as the top CM gene that is unable to be activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significantly activated contractility gene programs and signatures more similar to ventricular CMs. Human iCMs produced with MGT133+TBX20 more frequently demonstrated beating and calcium oscillation in co-culture with pluripotent stem cell derived CMs. More mitochondria and higher mitochondrial respiration were also detected in iCMs after TBX20 overexpression. Mechanistically, comprehensive transcriptomic, chromatin occupancy and epigenomic integration revealed that TBX20 localized to the cis-regulatory enhancers of under-expressed cardiac genes, such as MYBPC3, MYH7 and MYL4, to activate gene expression via strengthening the occupancy and co-occupancy of transcription factors. Furthermore, we identified TBX20-regulated enhancers and confirmed the synergistic effect of MGT and TBX20 on enhancer activation. Conclusions: TBX20 promotes cardiac cell fate conversion via direct activating cardiac enhancers. Human iCMs generated with TBX20 showed enhanced cardiac function in terms of contractility and mitochondrial respiration.
2022-09-14 | GSE193788 | GEO
Project description:Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). Results: To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human iCMs and functional cardiomyocytes (CMs). We identified T-box transcription factor TBX20 as the top CM gene that is unable to be activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significantly activated contractility gene programs and signatures more similar to ventricular CMs. Human iCMs produced with MGT133+TBX20 more frequently demonstrated beating and calcium oscillation in co-culture with pluripotent stem cell derived CMs. More mitochondria and higher mitochondrial respiration were also detected in iCMs after TBX20 overexpression. Mechanistically, comprehensive transcriptomic, chromatin occupancy and epigenomic integration revealed that TBX20 localized to the cis-regulatory enhancers of under-expressed cardiac genes, such as MYBPC3, MYH7 and MYL4, to activate gene expression via strengthening the occupancy and co-occupancy of transcription factors. Furthermore, we identified TBX20-regulated enhancers and confirmed the synergistic effect of MGT and TBX20 on enhancer activation. Conclusions: TBX20 promotes cardiac cell fate conversion via direct activating cardiac enhancers. Human iCMs generated with TBX20 showed enhanced cardiac function in terms of contractility and mitochondrial respiration.
2022-09-14 | GSE193908 | GEO
Project description:Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). Results: To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human iCMs and functional cardiomyocytes (CMs). We identified T-box transcription factor TBX20 as the top CM gene that is unable to be activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significantly activated contractility gene programs and signatures more similar to ventricular CMs. Human iCMs produced with MGT133+TBX20 more frequently demonstrated beating and calcium oscillation in co-culture with pluripotent stem cell derived CMs. More mitochondria and higher mitochondrial respiration were also detected in iCMs after TBX20 overexpression. Mechanistically, comprehensive transcriptomic, chromatin occupancy and epigenomic integration revealed that TBX20 localized to the cis-regulatory enhancers of under-expressed cardiac genes, such as MYBPC3, MYH7 and MYL4, to activate gene expression via strengthening the occupancy and co-occupancy of transcription factors. Furthermore, we identified TBX20-regulated enhancers and confirmed the synergistic effect of MGT and TBX20 on enhancer activation. Conclusions: TBX20 promotes cardiac cell fate conversion via direct activating cardiac enhancers. Human iCMs generated with TBX20 showed enhanced cardiac function in terms of contractility and mitochondrial respiration.
2022-09-14 | GSE193809 | GEO
Project description:Background: Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as one of the promising strategies to remuscularize the injured myocardium. Yet, it is still insufficient to generate functional induced cardiomyocytes (iCMs) from human fibroblasts using conventional reprogramming cocktails, such as our previously published combination consisting of MEF2C, GATA4, TBX5 and microRNA miR-133 (MGT133). Results: To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human iCMs and functional cardiomyocytes (CMs). We identified T-box transcription factor TBX20 as the top CM gene that is unable to be activated by MGT133. TBX20 is required for normal heart development and cardiac function in adult CMs but its role on cardiac reprogramming remains undefined. Here, we found that transduction of MGT133+TBX20 in human cardiac fibroblasts resulted in enhanced reprogramming featured with significantly activated contractility gene programs and signatures more similar to ventricular CMs. Human iCMs produced with MGT133+TBX20 more frequently demonstrated beating and calcium oscillation in co-culture with pluripotent stem cell derived CMs. More mitochondria and higher mitochondrial respiration were also detected in iCMs after TBX20 overexpression. Mechanistically, comprehensive transcriptomic, chromatin occupancy and epigenomic integration revealed that TBX20 localized to the cis-regulatory enhancers of under-expressed cardiac genes, such as MYBPC3, MYH7 and MYL4, to activate gene expression via strengthening the occupancy and co-occupancy of transcription factors. Furthermore, we identified TBX20-regulated enhancers and confirmed the synergistic effect of MGT and TBX20 on enhancer activation. Conclusions: TBX20 promotes cardiac cell fate conversion via direct activating cardiac enhancers. Human iCMs generated with TBX20 showed enhanced cardiac function in terms of contractility and mitochondrial respiration.
2022-09-14 | GSE193791 | GEO