In vivo cardiac reprogramming by delivery of PHF7 [snATAC-seq multiome]
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ABSTRACT:
PROVIDER: PRJNA1126098 | ENA |
REPOSITORIES: ENA
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Project description:Cellular reprogramming of cardiac fibroblasts to cardiomyocytes following myocardial infarction (MI) is an attractive strategy to redirect the fibrotic response of the non-regenerative adult heart to a more functional myocardium. Current reprogramming strategies are inefficient or require an excess of factors in adult and human cells due to staunch epigenetic barriers. Recently, we identified the epigenetic factor PHF7 as a potent activating factor of in vitro adult fibroblast reprogramming through modification of chromatin accessibility at cardiac super-enhancers. Here, we report the ability of PHF7 to activate adult fibroblast reprogramming alongside minimal co-factors in vitro, and the efficacy of these cocktails in vivo following MI in mice. Further, delivery of PHF7 as a single factor to the mouse heart following MI induced reprogramming and improved cardiac function. Deployment of single nuclear multi-omics revealed that PHF7 induced fundamental changes in chromatin structure by enhancing accessibility at CTCF binding sites and inhibiting Jun/Fos transcription factor activity to permit reprogramming in the injured heart. Together, these data support the potential for epigenetic factors like PHF7 to achieve in vivo reprogramming in isolation when utilized in the appropriate niche.
2025-08-13 | GSE270267 | GEO
Project description:Cellular reprogramming of cardiac fibroblasts to cardiomyocytes following myocardial infarction (MI) is an attractive strategy to redirect the fibrotic response of the non-regenerative adult heart to a more functional myocardium. Current reprogramming strategies are inefficient or require an excess of factors in adult and human cells due to staunch epigenetic barriers. Recently, we identified the epigenetic factor PHF7 as a potent activating factor of in vitro adult fibroblast reprogramming through modification of chromatin accessibility at cardiac super-enhancers. Here, we report the ability of PHF7 to activate adult fibroblast reprogramming alongside minimal co-factors in vitro, and the efficacy of these cocktails in vivo following MI in mice. Further, delivery of PHF7 as a single factor to the mouse heart following MI induced reprogramming and improved cardiac function. Deployment of single nuclear multi-omics revealed that PHF7 induced fundamental changes in chromatin structure by enhancing accessibility at CTCF binding sites and inhibiting Jun/Fos transcription factor activity to permit reprogramming in the injured heart. Together, these data support the potential for epigenetic factors like PHF7 to achieve in vivo reprogramming in isolation when utilized in the appropriate niche.
2025-08-13 | GSE270268 | GEO
Project description:In vivo cardiac reprogramming by delivery of PHF7 [snRNA-seq multiome]
| PRJNA1126097 | ENA
Project description:Cellular reprogramming of cardiac fibroblasts to cardiomyocytes following myocardial infarction (MI) is an attractive strategy to redirect the fibrotic response of the non-regenerative adult heart to a more functional myocardium. Current reprogramming strategies are inefficient or require an excess of factors in adult and human cells due to staunch epigenetic barriers. Recently, we identified the epigenetic factor PHF7 as a potent activating factor of in vitro adult fibroblast reprogramming through modification of chromatin accessibility at cardiac super-enhancers. Here, we report the ability of PHF7 to activate adult fibroblast reprogramming alongside minimal co-factors in vitro, and the efficacy of these cocktails in vivo following MI in mice. Further, delivery of PHF7 as a single factor to the mouse heart following MI induced reprogramming and improved cardiac function. Deployment of single nuclear multi-omics revealed that PHF7 induced fundamental changes in chromatin structure by enhancing accessibility at CTCF binding sites and inhibiting Jun/Fos transcription factor activity to permit reprogramming in the injured heart. Together, these data support the potential for epigenetic factors like PHF7 to achieve in vivo reprogramming in isolation when utilized in the appropriate niche.
2025-08-13 | GSE270266 | GEO
Project description:In vivo cardiac reprogramming by delivery of PHF7
| PRJNA1126099 | ENA
Project description:Direct cardiac reprogramming of fibroblasts to cardiomyocytes presents an attractive therapeutic strategy to restore cardiac function following injury. Cardiac reprogramming was initially achieved through the overexpression of the transcription factors Gata4, Mef2c, and Tbx5 (GMT), and later, Hand2 (GHMT) and Akt1 (AGHMT) were found to further enhance this process. Yet, staunch epigenetic barriers severely limit the ability of these cocktails to reprogram adult fibroblasts. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the histone reader PHF7 as the most potent activating factor. Mechanistically, PHF7 localizes to cardiac super-enhancers in fibroblasts, and through cooperation with the SWI/SNF complex, increases chromatin accessibility and transcription factor binding at these sites. Importantly, PHF7 is the first epigenetic factor found to achieve efficient reprogramming in the absence of Gata4. Here, we highlight the underexplored necessity of cardiac epigenetic modifiers, such as PHF7, in harnessing chromatin remodeling complexes to overcome critical barriers to direct cardiac reprogramming.
2021-02-26 | GSE151328 | GEO
Project description:These samples are part of a study investigating cancer cell plasticity in colorectal cancer metastasis. Tumour microenvironment cell types and cancer cell states were identified using 10x Genomics Multiome (paired snRNA-seq + snATAC-seq). snATAC-seq data is uploaded here.
2025-04-22 | E-MTAB-13652 | biostudies-arrayexpress
Project description:Multiome RNA+ATAC on human PBMCs (snATAC-seq data)
| PRJEB52980 | ENA
Project description:Here, we performed multiome sequencing (snRNA-seq + snATAC-seq) of human fetal liver samples from 3 trisomy 21 (Ts21) and 3 healthy foetuses (median age 14 post-conception weeks). The data set is composed of approximately 60,000 CD45+ foetal liver cells.
2024-07-17 | E-MTAB-13070 | biostudies-arrayexpress
Project description:We generated Multiome RNA+ATAC data from the same cell from human PBMC. This served as a gold benchmark for a novel integration method for multi-omics data that we developed.
2021-12-02 | E-MTAB-11226 | biostudies-arrayexpress