The histone acetyltransferase HBO1 (KAT7) promotes efficient tip cell sprouting during angiogenesis

Development ◽  
2021 ◽  
Author(s):  
Zoe L. Grant ◽  
Peter F. Hickey ◽  
Waruni Abeysekera ◽  
Lachlan Whitehead ◽  
Sabrina M. Lewis ◽  
...  

Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling. Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.

2017 ◽  
Vol 31 (11) ◽  
pp. 4720-4733 ◽  
Author(s):  
Andreas Benn ◽  
Christian Hiepen ◽  
Marc Osterland ◽  
Christof Schütte ◽  
An Zwijsen ◽  
...  

2020 ◽  
Author(s):  
Bahti Zakirov ◽  
Georgios Charalambous ◽  
Irene M. Aspalter ◽  
Kelvin Van-Vuuren ◽  
Thomas Mead ◽  
...  

AbstractHow do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms utilize feedback between movement and sensing known as ‘sensorimotor coordination’ or ‘active perception’ to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of concept in silico/in vivo study demonstrating that filopodia (actin-rich, dynamic, finger like cell-membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of ‘tip cell’ selection during blood vessel formation (angiogenesis).We first validate simulation predictions in vivo with live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive (‘basal’) form of active perception and find evidence in support. By viewing cell behaviour in tissues through the ‘basal cognitive lens’ we acquire a fresh perspective on not only the well-studied tip cell selection process, revealing a hidden, yet vital, time-keeping role for filopodia, but on how to interpret and understand cell behaviour in general, opening up a myriad of new and exciting research directions.


2018 ◽  
Author(s):  
Xiaodan Wang ◽  
Zhenshuo Zhu ◽  
Xiaolong Wu ◽  
Hao Li ◽  
Tongtong Li ◽  
...  

ABSTRACTSpermatogenesis is an important physiological process associated with male infertility. But whether there are RNA editings (REs) and what’s the role of REs during the process are still unclear. In this study, we integrated published RNA-Seq datasets and established a landscape of REs during the development of mouse spermatogenesis. 7530 editing sites among all types of male germ cells were found, which enrich on some regions of chromosome, including chromosome 17 and both ends of chromosome Y. Totally, REs occur in 2012 genes during spermatogenesis, more than half of which harbor at two different sites of the same gene at least. We also found REs mainly occur in introns, coding regions (CDSs) and intergenic regions. Moreover, about half of the REs in CDSs can cause amino acids changes. Finally, based on our adult male Kunming mice, we verified that there is a non-synonymous A-to-I RNA editing site inCog3during spermatogenesis, which is conserved not only between species but also across tissues. In short, based on the power of integrating RNA-Seq datasets, we provided the landscape of REs and found their dynamic changes during mouse spermatogenesis. This research strategy is general for other types of sequencing datasets and biological problems.


2020 ◽  
pp. 92-107 ◽  
Author(s):  
A. I. Bakhtigaraeva ◽  
A. A. Stavinskaya

The article considers the role of trust in the economy, the mechanisms of its accumulation and the possibility of using it as one of the growth factors in the future. The advantages and disadvantages of measuring the level of generalized trust using two alternative questions — about trusting people in general and trusting strangers — are analyzed. The results of the analysis of dynamics of the level of generalized trust among Russian youth, obtained within the study of the Institute for National Projects in 10 regions of Russia, are presented. It is shown that there are no significant changes in trust in people in general during the study at university. At the same time, the level of trust in strangers falls, which can negatively affect the level of trust in the country as a whole, and as a result have negative effects on the development of the economy in the future. Possible causes of the observed trends and the role of universities are discussed. Also the question about the connection between the level of education and generalized trust in countries with different quality of the institutional environment is raised.


2020 ◽  
Author(s):  
Ana M. Figueiredo ◽  
Pedro Barbacena ◽  
Rita Ferreira ◽  
Ana Russo ◽  
Silvia Vaccaro ◽  
...  

2021 ◽  
Author(s):  
Mei Zheng ◽  
Jingchen Lin ◽  
Xingbei Liu ◽  
Wei Chu ◽  
Jinpeng Li ◽  
...  

Abstract Polyploidy occurs prevalently and plays an important role during plant speciation and evolution. This phenomenon suggests polyploidy could develop novel features that enable them to adapt wider range of environmental conditions compared with diploid progenitors. Bread wheat (Triticum aestivum L., BBAADD) is a typical allohexaploid species and generally exhibits greater salt tolerance than its tetraploid wheat progenitor (BBAA). However, little is known about the underlying molecular basis and the regulatory pathway of this trait. Here, we show that the histone acetyltransferase TaHAG1 acts as a crucial regulator to strengthen salt tolerance of hexaploid wheat. Salinity-induced TaHAG1 expression was associated with tolerance variation in polyploidy wheat. Overexpression, silencing and CRISPR-mediated knockout of TaHAG1 validated the role of TaHAG1 in salinity tolerance of wheat. TaHAG1 contributed to salt tolerance by modulating ROS production and signal specificity. Moreover, TaHAG1 directly targeted a subset of genes that are responsible for hydrogen peroxide production, and enrichment of TaHAG1 triggered increased H3 acetylation and transcriptional upregulation of these loci under salt stress. In addition, we found the salinity-induced TaHAG1-mediated ROS production pathway is involved in salt tolerance difference of wheat accessions with varying ploidy. Our findings provide insight into the molecular mechanism of how an epigenetic regulatory factor facilitates adaptability of polyploidy wheat and highlights this epigenetic modulator as a strategy for salt tolerance breeding in bread wheat.


2021 ◽  
pp. 074823372110155
Author(s):  
Weizhe Pan ◽  
Shengnan Yu ◽  
Jin Jia ◽  
Junyang Hu ◽  
Liang Jie ◽  
...  

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.


2021 ◽  
Vol 11 (14) ◽  
pp. 6301
Author(s):  
Giulia Grisolia ◽  
Mariarosa Astori ◽  
Antonio Ponzetto ◽  
Antonio Vercesi ◽  
Umberto Lucia

Recently, a non-equilibrium thermodynamic approach has been developed in order to model the fundamental role of the membrane electric potential in the cell behaviour. A related new viewpoint is introduced, with a design of a photobiomodulation treatment in order to restore part of the visual field. Here, a first step in experimental evidence of the validity of the thermodynamic approach is developed. This result represents the starting point for future experimental improvements for light stimulation in order to improve the quality of life of the patients. The future possible therapy will be in addition to the pharmacological treatments.


Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1007
Author(s):  
Divya Kattupalli ◽  
Asha Sreenivasan ◽  
Eppurathu Vasudevan Soniya

Black pepper (Piper nigrum L.) is a prominent spice that is an indispensable ingredient in cuisine and traditional medicine. Phytophthora capsici, the causative agent of footrot disease, causes a drastic constraint in P. nigrum cultivation and productivity. To counterattack various biotic and abiotic stresses, plants employ a broad array of mechanisms that includes the accumulation of pathogenesis-related (PR) proteins. Through a genome-wide survey, eleven PR-1 genes that belong to a CAP superfamily protein with a caveolin-binding motif (CBM) and a CAP-derived peptide (CAPE) were identified from P. nigrum. Despite the critical functional domains, PnPR-1 homologs differ in their signal peptide motifs and core amino acid composition in the functional protein domains. The conserved motifs of PnPR-1 proteins were identified using MEME. Most of the PnPR-1 proteins were basic in nature. Secondary and 3D structure analyses of the PnPR-1 proteins were also predicted, which may be linked to a functional role in P. nigrum. The GO and KEGG functional annotations predicted their function in the defense responses of plant-pathogen interactions. Furthermore, a transcriptome-assisted FPKM analysis revealed PnPR-1 genes mapped to the P. nigrum-P. capsici interaction pathway. An altered expression pattern was detected for PnPR-1 transcripts among which a significant upregulation was noted for basic PnPR-1 genes such as CL10113.C1 and Unigene17664. The drastic variation in the transcript levels of CL10113.C1 was further validated through qRT-PCR and it showed a significant upregulation in infected leaf samples compared with the control. A subsequent analysis revealed the structural details, phylogenetic relationships, conserved sequence motifs and critical cis-regulatory elements of PnPR-1 genes. This is the first genome-wide study that identified the role of PR-1 genes during P. nigrum-P. capsici interactions. The detailed in silico experimental analysis revealed the vital role of PnPR-1 genes in regulating the first layer of defense towards a P. capsici infection in Panniyur-1 plants.


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