Proteomic profiling of key transcription factors in the process of neonatal mouse cardiac regeneration capacity loss

2019 ◽  
Vol 43 (12) ◽  
pp. 1435-1442 ◽  
Author(s):  
Mangyuan Wang ◽  
ShengShou Hu ◽  
Yu Nie ◽  
Jiangping Song
Keyword(s):  
Transcription Factors ◽  
Cardiac Regeneration ◽  
Neonatal Mouse ◽  
Regeneration Capacity ◽  
Proteomic Profiling ◽  
Capacity Loss

Abstract 17185: Sympathetic Reinnervation is Required for Mammalian Cardiac Regeneration

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian A White ◽  
Julie Gordon ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Sympathetic Innervation ◽  
Cardiac Regeneration ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Mouse ◽  
Left Ventricular Myocardium ◽  
Autonomic Nerves ◽  
Mouse Heart ◽  
Minimal Scarring ◽  
Age Related

Rationale: Established animal models of tissue and limb regeneration demonstrate a critical dependence on concurrent reinnervation by the peripheral nervous system. The abundance of autonomic nerves in the mammalian heart suggests they play a similar role in the response to cardiac injury. Objective: To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. Methods and Results: Crossing Wnt1:cre transgenic mice with a double-tandem (td) tomato reporter strain identified all neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. Whole mount epi-fluorescence microscopy facilitated the clear resolution of subepicardial autonomic nerves in the mouse ventricles providing unprecedented detail of the subepicardial neuroanatomy of the mouse heart. We confirmed that sympathetic nerve structures envelop the entire heart, and importantly, exhibit robust re-growth into the regenerating myocardium following resection of the left ventricular apex in neonatal mice. While innervated hearts regenerate with minimal scarring to the left ventricular myocardium, we report that innate cardiac regeneration was inhibited following sympathectomy, as determined by cross-sectional percentage of viable LV myocardium (n=9, 0.87±1.4% vs. n=6, 14.05±4.4% ; p<0.01). Conclusions: Ablation of post-ganglionic sympathetic nerves blocks the innate regenerative capacity of neonatal mouse hearts. Therefore, the innate ability of the neonatal mouse heart to undergo regeneration in response to injury is dependent on sympathetic innervation of the ventricular myocardium. This finding has significant implications for adult regeneration following myocardial infarction where nerve growth is hindered by age related influences and scar tissue.

Abstract 35: Enhanced Reprogramming of Human Fibroblasts into Cardiomyocytes Using Minimal Transcription Factors

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yang Zhou ◽  
Sahar Alimohamadi ◽  
Jiandong Liu ◽  
Li Qian
Keyword(s):  
Transcription Factors ◽  
Disease Modeling ◽  
Human Fibroblasts ◽  
Cardiac Injury ◽  
Cardiac Regeneration ◽  
Clinical Applications ◽  
Significant Advance ◽  
Great Promise ◽  
Primary Fibroblasts ◽  
Core Components

The adult human heart has limited regenerative capacity and is thus an important target for novel regenerative approaches to replenish lost cardiomyocytes after cardiac injury. Cardiac reprogramming that converts fibroblasts to contractile induced cardiomyocytes (iCMs) by overexpressing cardiac lineage specific transcription factors holds great promise as an alternative approach for cardiac regeneration and disease modeling. Significant advance has been made to generate mouse iCMs; however, human iCM (hiCM) generation remains challenging and the yield is low for clinical applications. Here, we leveraged the knowledge that we learned from studying mouse iCM reprogramming to define the optimal condition for hiCM induction. We titrated the dosage of the human reprogramming factors systematically and surprisingly found the minimal core components GATA4, MEF2C and TBX5 were sufficient to induce cardiac fate in human primary fibroblasts. This is in sharp contrast to what has been reported in the literature. Subsequently, we cloned these three factors into a polycistronic vector separated by 2A peptides for defined ratio of protein expression. By optimizing the growth condition, we further improved the efficiency of hiCM reprogramming. Mechanistically, we found the balanced expression of this minimal combination of transcription factors with tailored microenvironment enhanced the establishment of cardiac program in non-myocytes. In sum, our study demonstrates that the use of a single vector with only three transcription factors simplifies generation and improves the yield of hiCMs for potential future clinical applications.

scholarly journals Proteomic Analysis of Trichoderma atroviride Reveals Independent Roles for Transcription Factors BLR-1 and BLR-2 in Light and Darkness

2011 ◽  
Vol 11 (1) ◽  
pp. 30-41 ◽  
Author(s):  
Alejandro Sánchez-Arreguín ◽  
Ana Silvia Pérez-Martínez ◽  
Alfredo Herrera-Estrella
Keyword(s):  
Transcription Factors ◽  
Blue Light ◽  
Light Pulse ◽  
Mechanical Damage ◽  
Pathogenic Fungi ◽  
Mrna Levels ◽  
Trichoderma Atroviride ◽  
Proteomic Profiling ◽  
Content Type ◽  
Protein Levels

ABSTRACT The genus Trichoderma is one of the most widely used biological control agents of plant-pathogenic fungi. The main mechanism for survival and dispersal of Trichoderma is through the production of asexual spores (conidia). The transition from filamentous growth to conidiation can be triggered by light, nutrient deprivation, and mechanical damage of the mycelium. We conducted proteomic profiling analyses of Trichoderma atroviride after a blue light pulse. The use of two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) analysis allowed us to identify 72 proteins whose expression was affected by blue light. Functional category analysis showed that the various proteins are involved in metabolism, cell rescue, and protein synthesis. We determined the relationship between mRNA levels of selected genes 30 min after a light pulse and protein expression levels at different times after the pulse and found this correlation to be very weak. The correlation was highest when protein and mRNA levels were compared for the same time point. The transcription factors BLR-1 and BLR-2 are vital to the photoconidiation process; here we demonstrate that both BLR proteins are active in darkness and affect several elements at both the transcript and protein levels. Unexpectedly, in darkness, downregulation of proteins prevailed in the Δ blr-1 mutant, while upregulation of proteins predominated in the Δ blr-2 mutant. Our data demonstrate that the BLR proteins play roles individually and as a complex.

scholarly journals E2F/Dp inactivation in fat body cells triggers systemic metabolic changes

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maria Paula Zappia ◽  
Ana Guarner ◽  
Nadia Kellie-Smith ◽  
Alice Rogers ◽  
Robert Morris ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Fat Body ◽  
Critical Role ◽  
Systemic Effects ◽  
Proteomic Profiling ◽  
Animal Development ◽  
Metabolomic Profiling ◽  
Essential Function ◽  
E2f Transcription Factors

The E2F transcription factors play a critical role in controlling cell fate. In Drosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently, rescued animal lethality. Collectively, our data highlight the unexpected complexity of E2F mutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development.

scholarly journals Transcriptomic and Proteomic Profiling Reveal the Key Role of AcMYB16 in the Response of Pseudomonas syringae pv. actinidiae in Kiwifruit

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojie Wang ◽  
Yawei Li ◽  
Yuanyuan Liu ◽  
Dongle Zhang ◽  
Min Ni ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pseudomonas Syringae ◽  
Regulatory Element ◽  
Differentially Expressed ◽  
Resistant Cultivar ◽  
Proteomic Profiling ◽  
Phenylpropanoid Biosynthesis ◽  
R2r3 Myb ◽  
Important Disease

Kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa), is an important disease of kiwifruit (Actinidia Lind.). Plant hormones may induce various secondary metabolites to resist pathogens via modulation of hormone-responsive transcription factors (TFs), as reported in past studies. In this study, we showed that JA accumulated in the susceptible cultivar Actinidia chinensis ‘Hongyang’ but decreased in the resistant cultivar of A. chinensis var. deliciosa ‘Jinkui’ in response to Psa. Integrated transcriptomic and proteomic analyses were carried out using the resistant cultivar ‘Jinkui’. A total of 5,045 differentially expressed genes (DEGs) and 1,681 differentially expressed proteins (DEPs) were identified after Psa infection. Two pathways, ‘plant hormone signal transduction’ and ‘phenylpropanoid biosynthesis,’ were activated at the protein and transcript levels. In addition, a total of 27 R2R3-MYB transcription factors (TFs) were involved in the response to Psa of ‘Jinkui,’ including the R2R3-MYB TF subgroup 4 gene AcMYB16, which was downregulated in ‘Jinkui’ but upregulated in ‘Hongyang.’ The promoter region of AcMYB16 has a MeJA responsiveness cis-acting regulatory element (CRE). Transient expression of the AcMYB16 gene in the leaves of ‘Jinkui’ induced Psa infection. Together, these data suggest that AcMYB16 acts as a repressor to regulate the response of kiwifruit to Psa infection. Our work will help to unravel the processes of kiwifruit resistance to pathogens and will facilitate the development of varieties with resistance against bacterial pathogens.

The roles of signaling pathways in cardiac regeneration

2021 ◽  
Vol 28 ◽  
Author(s):  
Amir Valizadeh ◽  
Samira Asghari ◽  
Parinaz Mansouri ◽  
Forough Alemi ◽  
Maryam Majidinia ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Animal Species ◽  
Cell Communication ◽  
Cardiac Regeneration ◽  
Cardiac Repair ◽  
Regeneration Capacity ◽  
Disease Treatment ◽  
Model Studies ◽  
Vegf Signaling

: In recent years, knowledge of cardiac regeneration mechanisms has dramatically expanded. Regeneration can replace lost parts of organs, common among animal species. The heart is commonly considered an organ with terminal development, which has no reparability potential during post-natal life; however, some intrinsic regeneration capacity has been reported for cardiac muscle, which opens novel avenues in cardiovascular disease treatment. Different endogenous mechanisms were studied for cardiac repairing and regeneration in recent decades. Survival, proliferation, inflammation, angiogenesis, cell-cell communication, cardiomyogenesis, and anti-aging pathways are the most important mechanisms that have been studied in this regard. Several in vitro and animal model studies focused on proliferation induction for cardiac regeneration reported promising results. These studies have mainly focused on promoting proliferation signaling pathways and demonstrated various signaling pathways such as Wnt, PI3K/Akt, IGF-1, TGF-β, Hippo, and VEGF signaling cardiac regeneration. Therefore, in this review, we intended to discuss the connection between different critical signaling pathways in cardiac repair and regeneration.

scholarly journals E2F/Dp inactivation in fat body cells triggers systemic metabolic changes

2021 ◽  
Author(s):  
Maria Paula Zappia ◽  
Ana Guarner ◽  
Nadia Kellie-Smith ◽  
Alice Rogers ◽  
Robert Morris ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Fat Body ◽  
Critical Role ◽  
Systemic Effects ◽  
Proteomic Profiling ◽  
Animal Development ◽  
Metabolomic Profiling ◽  
Essential Function ◽  
E2f Transcription Factors

ABSTRACTThe E2F transcription factors play a critical role in controlling cell fate. In Drosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently, rescued animal lethality. Collectively, our data highlight the unexpected complexity of E2F mutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development.

Sign in / Sign up

Export Citation Format

Share Document