The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming

Garry, Glynnis A.; Bezprozvannaya, Svetlana; Chen, Kenian; Zhou, Huanyu; Hashimoto, Hisayuki; Morales, María Gabriela; Liu, Ning; Bassel‐Duby, Rhonda; Olson, Eric N.

doi:10.1038/s41556-021-00668-z

Cited by 51 publications

(38 citation statements)

References 38 publications

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“…More recently, direct cardiac reprogramming protocols have been refined by integrating GMT overexpression with the modulation of polycomb repressive chromatin remodeling complexes 1 (PRC1) [92,93] or 2 (PRC2) [94,95].…”

Section: Direct Cardiac Reprogramming Approachmentioning

confidence: 99%

MicroRNA Roles in Cell Reprogramming Mechanisms

Pascale

Caiazza

Paladino

et al. 2022

Cells

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Cell reprogramming is a groundbreaking technology that, in few decades, generated a new paradigm in biomedical science. To date we can use cell reprogramming to potentially generate every cell type by converting somatic cells and suitably modulating the expression of key transcription factors. This approach can be used to convert skin fibroblasts into pluripotent stem cells as well as into a variety of differentiated and medically relevant cell types, including cardiomyocytes and neural cells. The molecular mechanisms underlying such striking cell phenotypes are still largely unknown, but in the last decade it has been proven that cell reprogramming approaches are significantly influenced by non-coding RNAs. Specifically, this review will focus on the role of microRNAs in the reprogramming processes that lead to the generation of pluripotent stem cells, neurons, and cardiomyocytes. As highlighted here, non-coding RNA-forced expression can be sufficient to support some cell reprogramming processes, and, therefore, we will also discuss how these molecular determinants could be used in the future for biomedical purposes.

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Section: Direct Cardiac Reprogramming Approachmentioning

confidence: 99%

MicroRNA Roles in Cell Reprogramming Mechanisms

Pascale

Caiazza

Paladino

et al. 2022

Cells

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“…The changes in chromatin accessibility were also due to the interaction of PHF7 with the cardiacspecific SWI/SNF subunit Smarcd3/BAF60C. Additionally, PHF7 was found to enhance reprogramming of adult human CFs, inducing a~threefold increase in reprogramming above the MYOCD-containing human reprogramming cocktail alone [131].…”

Section: Strategies For In Vitro Direct Cardiac Reprogrammingmentioning

confidence: 94%

“…Very recently, Garry et al demonstrated that overexpression of the histone reader PHD Finger Protein 7 (PHF7) in mouse tail-tip fibroblasts (TTFs) generated a 10-fold increase of iCM with respect to AGHMT alone [131]. PHF7 with MEF2C and TBX5 alone induced the reprogramming of TTFs to iCMs in the absence of GATA4 by binding to multivalent cardiac super-enhancers through the recognition of H3K4me2/3 marks and increasing the chromatin accessibility and the binding of MEF2C and TBX5 at these sites [131]. The changes in chromatin accessibility were also due to the interaction of PHF7 with the cardiacspecific SWI/SNF subunit Smarcd3/BAF60C.…”

Section: Strategies For In Vitro Direct Cardiac Reprogrammingmentioning

confidence: 99%

Advanced Technologies to Target Cardiac Cell Fate Plasticity for Heart Regeneration

Testa

Benedetto

Passaro

2021

IJMS

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The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.

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“…However, it was shown that endogenous cardiac transcription factor activation is necessary for expression of maturation genes but not sufficient to induce efficient cardiac fibroblast transdifferentiation (108). It will be interesting to evaluate whether combinatorial activation and/or repression, allowing for more precise control of multiple pathways in orthogonal directions, could enhance cardiomyocytes reprogramming efficiencies by harnessing knowledge about the epigenetic landscape and modulating factors of cardiomyogenic cells (109).…”

Section: Crispr-mediated Control Of Transcription To Enhance Cardiac ...mentioning

confidence: 99%

Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine

Schoger

Panàkovà

Zelarayán

2022

Front. Cardiovasc. Med.

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Molecular and genetic differences between individual cells within tissues underlie cellular heterogeneities defining organ physiology and function in homeostasis as well as in disease states. Transcriptional control of endogenous gene expression has been intensively studied for decades. Thanks to a fast-developing field of single cell genomics, we are facing an unprecedented leap in information available pertaining organ biology offering a comprehensive overview. The single-cell technologies that arose aided in resolving the precise cellular composition of many organ systems in the past years. Importantly, when applied to diseased tissues, the novel approaches have been immensely improving our understanding of the underlying pathophysiology of common human diseases. With this information, precise prediction of regulatory elements controlling gene expression upon perturbations in a given cell type or a specific context will be realistic. Simultaneously, the technological advances in CRISPR-mediated regulation of gene transcription as well as their application in the context of epigenome modulation, have opened up novel avenues for targeted therapy and personalized medicine. Here, we discuss the fast-paced advancements during the recent years and the applications thereof in the context of cardiac biology and common cardiac disease. The combination of single cell technologies and the deep knowledge of fundamental biology of the diseased heart together with the CRISPR-mediated modulation of gene regulatory networks will be instrumental in tailoring the right strategies for personalized and precision medicine in the near future. In this review, we provide a brief overview of how single cell transcriptomics has advanced our knowledge and paved the way for emerging CRISPR/Cas9-technologies in clinical applications in cardiac biomedicine.

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The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming

Cited by 51 publications

References 38 publications

MicroRNA Roles in Cell Reprogramming Mechanisms

MicroRNA Roles in Cell Reprogramming Mechanisms

Advanced Technologies to Target Cardiac Cell Fate Plasticity for Heart Regeneration

Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine

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