Nkx2.5 Based Ventricular Programming of Murine ESC-Derived Cardiomyocytes

Thiele, Frauke; Voelkner, Christin; Krebs, Vivien; Müller, Paula; Jung, Julia Jeannine; Rimmbach, Christian; Steinhoff, Gustav; Noack, Thomas; Dávid, Róbert; Lemcke, Heiko

doi:10.33594/000000142

Cited by 9 publications

(4 citation statements)

References 66 publications

(96 reference statements)

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“…Hence, there is a need for methods that allow monitoring of cardiac maturity in order to improve culture conditions that facilitate proper cardiac development. Moreover, these techniques can help to control the efficiency of stem cell and somatic cell (re-)programming strategies aiming towards the generation of cardiomyocytes from various cell types [7][8][9] The maturation process of iPSC CM involves several developmental changes of cellular function and physiology, including metabolic switch, electrophysiological and molecular transformation, and changes of mechanical behavior [10,11]. Moreover, structural organization of the contractile machinery is critical during cardiac maturation as it mediates force generation and cell contraction [1].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Evaluation of the Sarcomere Network of Human hiPSC-Derived Cardiomyocytes Using Single-Molecule Localization Microscopy

Lemcke

Skorska

Lang

et al. 2020

IJMS

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The maturation of iPSC-derived cardiomyocytes is still a critical point for their application in cardiovascular research as well as for their clinical use. Although multiple differentiation protocols have been established, researchers failed to generate fully mature cardiomyocytes in vitro possessing identical phenotype-related and functional properties as their native adult counterparts. Besides electrophysiological and metabolic changes, the establishment of a well structured sarcomere network is important for the development of a mature cardiac phenotype. Here, we present a super resolution-based approach to quantitatively evaluate the structural maturation of iPSC-derived cardiomyocytes. Fluorescence labelling of the α-actinin cytoskeleton and subsequent visualization by photoactivated localization microscopy allows the acquisition of highly resolved images for measuring sarcomere length and z-disc thickness. Our image analysis revealed that iPSC and neonatal cardiomyocyte share high similarity with respect to their sarcomere organization, however, contraction capacity was inferior in iPSC-derived cardiac cells, indicating an early maturation level. Moreover, we demonstrate that this imaging approach can be used as a tool to monitor cardiomyocyte integrity, helping to optimize iPSC differentiation as well as somatic cell direct-reprogramming strategies.

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Section: Introductionmentioning

confidence: 99%

Quantitative Evaluation of the Sarcomere Network of Human hiPSC-Derived Cardiomyocytes Using Single-Molecule Localization Microscopy

Lemcke

Skorska

Lang

et al. 2020

IJMS

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“…The stimulation of CM synthesis in injured myocardium depends on the reactivation of genes vital during cardiogenesis ( 85 ). The exogenous overexpression of Nkx2.5 in cardiomyocytes derived from ESCs resulted in the development of monocytes with characteristics of early ventricular cardiomyocytes, including the expression of sarcomeric markers, spontaneous beating frequency, and distinct occurrence of L-type calcium channels ( 86 ). These findings support the potential of Nkx2.5 overexpression as a strategy for inducing early cardiomyocyte differentiation.…”

Section: Potential Of Nkx25 In Cardiac Regenerationmentioning

confidence: 99%

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases

Cao,

Li,

Zhang

et al. 2023

Front. Cardiovasc. Med.

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Cardiomyocytes fail to regenerate after birth and respond to mitotic signals through cellular hypertrophy rather than cellular proliferation. Necrotic cardiomyocytes in the infarcted ventricular tissue are eventually replaced by fibroblasts, generating scar tissue. Cardiomyocyte loss causes localized systolic dysfunction. Therefore, achieving the regeneration of cardiomyocytes is of great significance for cardiac function and development. Heart development is a complex biological process. An integral cardiac developmental network plays a decisive role in the regeneration of cardiomyocytes. During this process, genetic epigenetic factors, transcription factors, signaling pathways and small RNAs are involved in regulating the developmental process of the heart. Cardiomyocyte-specific genes largely promote myocardial regeneration, among which the Nkx2.5 transcription factor is one of the earliest markers of cardiac progenitor cells, and the loss or overexpression of Nkx2.5 affects cardiac development and is a promising candidate factor. Nkx2.5 affects the development and function of the heart through its multiple functional domains. However, until now, the specific mechanism of Nkx2.5 in cardiac development and regeneration is not been fully understood. Therefore, this article will review the molecular structure, function and interaction regulation of Nkx2.5 to provide a new direction for cardiac development and the treatment of heart regeneration.

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“…Accordingly, a safer approach is warranted to minimize reperfusion injury in myocardial infarction. Nkx2.5 is an early cardiovascular transcription factor ( Thiele et al, 2019 ), and its specific deletion can lead to cardiac abnormalities( He et al, 2022 ), suggesting the importance of Nkx2.5 for heart development and growth. Continuous Baicalin treatment can induce functional myocardium formation of embryonic stem cell line D3 by up-regulating the transcription of Nkx2.5 at the intermediate and late stages of differentiation ( Tang et al, 2013 ) ( Figure 2A ).…”

Section: Baicalin and Embryonic Stem Cellsmentioning

confidence: 99%

Baicalin regulates stem cells as a creative point in the treatment of climacteric syndrome

et al. 2022

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Nkx2.5 Based Ventricular Programming of Murine ESC-Derived Cardiomyocytes

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 9 publications

References 66 publications

Quantitative Evaluation of the Sarcomere Network of Human hiPSC-Derived Cardiomyocytes Using Single-Molecule Localization Microscopy

Quantitative Evaluation of the Sarcomere Network of Human hiPSC-Derived Cardiomyocytes Using Single-Molecule Localization Microscopy

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases

Baicalin regulates stem cells as a creative point in the treatment of climacteric syndrome

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