Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation

Uosaki, Hideki; Taguchi, Y-h.

doi:10.1016/j.gpb.2016.04.004

Cited by 45 publications

(39 citation statements)

References 28 publications

(40 reference statements)

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“…This suggests that the machinery needed for CM maturation might be conserved in rodents and humans. In fact, although rodents have a shorter lifespan, comparative transcriptional analyses revealed that genes involved in mouse CM maturation are similarly regulated during human heart maturation (Uosaki and Taguchi, 2016). It will be interesting to test if hPSC-CMs can also be matured in larger animal models.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

et al. 2017

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SUMMARY Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of the transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which predominantly manifests in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

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Section: Discussionmentioning

confidence: 99%

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

et al. 2017

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“…Identifying the genes involved in human cardiomyocytes maturation is still an ongoing process. But the overall expression pattern of maturation-related genes identified in mice and humans are mostly similar (DeLaughter et al, 2016;Uosaki and Taguchi, 2016). Isoform transitions of sarcomeric genes occur from fetal to adult period.…”

Section: Gene Expressionmentioning

confidence: 99%

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes

Ahmed¹,

Anzai²,

Chanthra³

et al. 2020

Front. Cell Dev. Biol.

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Cardiovascular diseases are the leading cause of death worldwide. Therefore, the discovery of induced pluripotent stem cells (iPSCs) and the subsequent generation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) was a pivotal point in regenerative medicine and cardiovascular research. They constituted an appealing tool for replacing dead and dysfunctional cardiac tissue, screening cardiac drugs and toxins, and studying inherited cardiac diseases. The problem is that these cells remain largely immature, and in order to utilize them, they must reach a functional degree of maturity. To attempt to mimic in vivo environment, various methods including prolonging culture time, co-culture and modulations of chemical, electrical, mechanical culture conditions have been tried. In addition to that, changing the topology of the culture made huge progress with the introduction of the 3D culture that closely resembles the in vivo cardiac topology and overcomes many of the limitations of the conventionally used 2D models. Nonetheless, 3D culture alone is not enough, and using a combination of these methods is being explored. In this review, we summarize the main differences between immature, fetal-like hiPSC-CMs and adult cardiomyocytes, then glance at the current approaches used to promote hiPSC-CMs maturation. In the second part, we focus on the evolving 3D culture model-it's structure, the effect on hiPSC-CMs maturation, incorporation with different maturation methods, limitations and future prospects.

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“…Thereby, data sets of several knock-out and knock-in mouse models [13][14][15] have been useful to validate data. Differences between mouse and human signaling cascades have been observed in several cell types including platelets [16][17][18]. Therefore, systematic analyses of mouse and human platelet signaling cascades are required to estimate limitations of transferability of generated results and stress human speci cs including potential therapeutic targets.…”

Section: Methods Of Bioinformatics Have Already Been Used To Simulatementioning

confidence: 99%

Comparison of the central human and mouse platelet signaling cascade by systems biological analysis

Balkenhol

Kaltdorf

Mammadova‐Bach

et al. 2020

Preprint

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Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always uniprot notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signalling differences.

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Comparative Gene Expression Analysis of Mouse and Human Cardiac Maturation

Cited by 45 publications

References 28 publications

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes

Comparison of the central human and mouse platelet signaling cascade by systems biological analysis

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