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Author Mingxia Gu

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Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates

Andrea Toth, Shelby Steinmeyer, Paranthaman Kannan, Jerilyn Gray, Courtney Jackson, Shibabrata Mukherjee, Martin Demmert, Joshua Sheak, Daniel Benson, Joe Kitzmiller, Joseph Wayman, Pietro Presicce, Christopher Cates, Rhea Rubin, Kashish Chetal, Yina Du, Yifei Miao, Mingxia Gu, Minzhe Guo, Vladimir Kalinichenko, Suhas Kallapur, Emily Miraldi, Yan Xu, Daniel Swarr, Ian Lewkowich, Nathan Salomonis, Lisa Miller, Jennifer Sucre, Jeffrey Whitsett, Claire Chougnet, Alan Jobe, Hitesh Deshmukh, William Zacharias,

Malformations of or injuries to the developing lung are associated with perinatal morbidity and mortality with lifelong consequences for subsequent pulmonary health. One fetal exposure linked with poor health outcomes is chorioamnionitis, which impacts up to 25-40% of preterm births. Severe chorioamnionitis with prematurity is associated with significantly increased risk ... Read more >>

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Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.

Miranda K Culley, Jingsi Zhao, Yi Yin Tai, Ying Tang, Dror Perk, Vinny Negi, Qiujun Yu, Chen-Shan C Woodcock, Adam Handen, Gil Speyer, Seungchan Kim, Yen-Chun Lai, Taijyu Satoh, Annie Mm Watson, Yassmin Al Aaraj, John Sembrat, Mauricio Rojas, Dmitry Goncharov, Elena A Goncharova, Omar F Khan, Daniel G Anderson, James E Dahlman, Aditi U Gurkar, Robert Lafyatis, Ahmed U Fayyaz, Margaret M Redfield, Mark T Gladwin, Marlene Rabinovitch, Mingxia Gu, Thomas Bertero, Stephen Y Chan,

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2021, 131(11):]

Cited: 1 time

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iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension.

Mingxia Gu, Michele Donato, Minzhe Guo, Neil Wary, Yifei Miao, Shuai Mao, Toshie Saito, Shoichiro Otsuki, Lingli Wang, Rebecca L Harper, Silin Sa, Purvesh Khatri, Marlene Rabinovitch,

Pulmonary arterial hypertension (PAH) is a progressive disorder leading to occlusive vascular remodeling. Current PAH therapies improve quality of life but do not reverse structural abnormalities in the pulmonary vasculature. Here, we used high-throughput drug screening combined with in silico analyses of existing transcriptomic datasets to identify a promising lead ... Read more >>

Sci Transl Med (Science translational medicine)
[2021, 13(592):]

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Endogenous Retroviral Elements Generate Pathologic Neutrophils and Elastase Rich Exosomes in Pulmonary Arterial Hypertension

Shalina Taylor, Kévin Contrepois, Bérénice Benayoun, Lihua Jiang, Sarasa Isobe, Lingli Wang, Stavros Melemenidis, Mehmet Ozen, Shoichiro Otsuki, Tsutomu Shinohara, Andrew Sweatt, Jordan Kaplan, Aiqin Cao, Jan-Renier Moonen, David Marciano, Mingxia Gu, Kazuya Miyagawa, Patricia Del Rosario, Andrew Hsi, Roger Thompson, Maria-Eugenia Ariza, Utkan Demirci, Roham Zamanian, Francois Haddad, Mark Nicolls, Michael Snyder, Marlene Rabinovitch,

<h4>ABSTRACT</h4> Neutrophil elastase (NE) is implicated in pulmonary arterial hypertension (PAH) but the role of neutrophils in the pathogenesis of PAH is unclear. Here we show that neutrophils from PAH vs. control subjects produce and release increased NE associated with enhanced extracellular trap formation. PAH neutrophils are highly adherent and ... Read more >>

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BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors.

Alexander A Mikryukov, Amine Mazine, Bei Wei, Donghe Yang, Yifei Miao, Mingxia Gu, Gordon M Keller,

The embryonic endocardium is essential for early heart development as it functions to induce trabecular myocardium, the first heart tissue to form, and is the source of the cells that make up the valves and a portion of the coronary vasculature. With this potential, human endocardial cells could provide unique ... Read more >>

Cell Stem Cell (Cell stem cell)
[2021, 28(1):96-111.e7]

Cited: 3 times

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Patient-Specific Induced Pluripotent Stem Cells Implicate Intrinsic Impaired Contractility in Hypoplastic Left Heart Syndrome.

Sharon L Paige, Francisco X Galdos, Soah Lee, Elizabeth T Chin, Sara Ranjbarvaziri, Dries A M Feyen, Adrija K Darsha, Sidra Xu, Julia A Ryan, Aimee L Beck, M Yasir Qureshi, Yifei Miao, Mingxia Gu, Daniel Bernstein, Timothy J Nelson, Mark Mercola, Marlene Rabinovitch, Euan A Ashley, Victoria N Parikh, Sean M Wu,

Circulation (Circulation)
[2020, 142(16):1605-1608]

Cited: 4 times

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Capillary cell-type specialization in the alveolus.

Astrid Gillich, Fan Zhang, Colleen G Farmer, Kyle J Travaglini, Serena Y Tan, Mingxia Gu, Bin Zhou, Jeffrey A Feinstein, Mark A Krasnow, Ross J Metzger,

In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood<sup>1</sup>. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries ... Read more >>

Nature (Nature)
[2020, 586(7831):785-789]

Cited: 8 times

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Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome.

Yifei Miao, Lei Tian, Marcy Martin, Sharon L Paige, Francisco X Galdos, Jibiao Li, Alyssa Klein, Hao Zhang, Ning Ma, Yuning Wei, Maria Stewart, Soah Lee, Jan-Renier Moonen, Bing Zhang, Paul Grossfeld, Seema Mital, David Chitayat, Joseph C Wu, Marlene Rabinovitch, Timothy J Nelson, Shuyi Nie, Sean M Wu, Mingxia Gu,

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by abnormalities in the left ventricle, associated valves, and ascending aorta. Studies have shown intrinsic myocardial defects but do not sufficiently explain developmental defects in the endocardial-derived cardiac valve, septum, and vasculature. Here, we identify a developmentally impaired ... Read more >>

Cell Stem Cell (Cell stem cell)
[2020, 27(4):574-589.e8]

Cited: 9 times

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Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.

Kitchener D Wilson, Mohamed Ameen, Hongchao Guo, Oscar J Abilez, Lei Tian, Maxwell R Mumbach, Sebastian Diecke, Xulei Qin, Yonggang Liu, Huaxiao Yang, Ning Ma, Sadhana Gaddam, Nathan J Cunningham, Mingxia Gu, Evgenios Neofytou, Maricela Prado, Thomas B Hildebrandt, Ioannis Karakikes, Howard Y Chang, Joseph C Wu,

Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we ... Read more >>

Dev Cell (Developmental cell)
[2020, 54(6):694-709.e9]

Cited: 3 times

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MicroRNA-483 amelioration of experimental pulmonary hypertension.

Jin Zhang, Yangyang He, Xiaosong Yan, Shanshan Chen, Ming He, Yuyang Lei, Jiao Zhang, Brendan Gongol, Mingxia Gu, Yifei Miao, Liang Bai, Xiaopei Cui, Xiaojian Wang, Yixin Zhang, Fenling Fan, Zhao Li, Yuan Shen, Chih-Hung Chou, Hsien-Da Huang, Atul Malhotra, Marlene Rabinovitch, Zhi-Cheng Jing, John Y-J Shyy,

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed ... Read more >>

EMBO Mol Med (EMBO molecular medicine)
[2020, 12(5):e11303]

Cited: 2 times

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Isolation of Endocardial and Coronary Endothelial Cells from the Ventricular Free Wall of the Rat Heart.

Alyssa Klein, Bethel Bayrau, Yifei Miao, Mingxia Gu,

It has been shown that endocardial endothelial cells (EECs) and coronary endothelial cells (CECs) differ in origin, development, markers, and functions. Consequently, these two cell populations play unique roles in cardiac diseases. Current studies involving isolated endothelial cells investigate cell populations consisting of both EECs and CECs. This protocol outlines ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2020, (158):]

Cited: 1 time

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Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension.

Armando Reyes-Palomares, Mingxia Gu, Fabian Grubert, Ivan Berest, Silin Sa, Maya Kasowski, Christian Arnold, Mao Shuai, Rohith Srivas, Simon Miao, Dan Li, Michael P Snyder, Marlene Rabinovitch, Judith B Zaugg,

Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):1673]

Cited: 8 times

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Single-Cell RNA-Seq Reveals Endocardial Defect in Hypoplastic Left Heart Syndrome

Yifei Miao, Lei Tian, Marcy Martin, Sharon Paige, Francisco Galdos, Jibiao Li, Alyssa Guttman, Yuning Wei, Jan-Renier Moonen, Hao Zhang, Ning Ma, Bing Zhang, Paul Grossfeld, Seema Mital, David Chitayat, Joseph Wu, Marlene Rabinovitch, Timothy Nelson, Shuyi Nie, Sean Wu, Mingxia Gu,

<h4>Summary</h4> Hypoplastic left heart syndrome (HLHS) is one of the most challenging forms of congenital heart diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain the abnormal development of the cardiac valve, septum, and vasculature, known to originate from the endocardium. Here, ... Read more >>

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Generation of Quiescent Cardiac Fibroblasts From Human Induced Pluripotent Stem Cells for In Vitro Modeling of Cardiac Fibrosis.

Hao Zhang, Lei Tian, Mengcheng Shen, Chengyi Tu, Haodi Wu, Mingxia Gu, David T Paik, Joseph C Wu,

<h4>Rationale</h4>Activated fibroblasts are the major cell type that secretes excessive extracellular matrix in response to injury, contributing to pathological fibrosis and leading to organ failure. Effective anti-fibrotic therapeutic solutions, however, are not available due to the poorly defined characteristics and unavailability of tissue-specific fibroblasts. Recent advances in single-cell RNA-sequencing fill ... Read more >>

Circ Res (Circulation research)
[2019, 125(5):552-566]

Cited: 17 times

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Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells.

Mingxia Gu,

Endothelial cells (ECs) line the interior surface of blood and lymphatic vessels, and play a key role in a variety of physiological or pathological processes such as thrombosis, inflammation, or vascular wall remodeling. Human-induced pluripotent stem cell (iPSCs)-derived ECs provide a new opportunity for vascular regeneration and serve as a ... Read more >>

Curr Protoc Hum Genet (Current protocols in human genetics)
[2018, :e64]

Cited: 4 times

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Small-conductance Ca2+-activated K+ channels: insights into their roles in cardiovascular disease.

Mingxia Gu, Yanrong Zhu, Xiaorong Yin, Dai-Min Zhang,

Life-threatening malignant arrhythmias in pathophysiological conditions can increase the mortality and morbidity of patients with cardiovascular diseases. Cardiac electrical activity depends on the coordinated propagation of excitatory stimuli and the generation of action potentials in cardiomyocytes. Action potential formation results from the opening and closing of ion channels. Recent studies ... Read more >>

Exp Mol Med (Experimental & molecular medicine)
[2018, 50(4):1-7]

Cited: 3 times

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MiR-147b inhibits cell viability and promotes apoptosis of rat H9c2 cardiomyocytes via down-regulating KLF13 expression.

Mingxia Gu, Jing Wang, Yi Wang, Yanjuan Xu, Yingqiang Zhang, Weiqing Wu, Shuping Liao,

Recently, microRNAs (miRNAs) have been shown to involve in the process of heart failure. This study aims to investigate the functional role of miR-147b in rat H9c2 cardiomyocytes and explore the underlying molecular mechanisms. Cell viability of H9c2 cells was detected by MTT assay. Cell apoptosis was detected by flow ... Read more >>

Acta Biochim Biophys Sin (Shanghai) (Acta biochimica et biophysica Sinica)
[2018, 50(3):288-297]

Cited: 5 times

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Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.

Toshie Saito, Kazuya Miyagawa, Shih-Yu Chen, Rasa Tamosiuniene, Lingli Wang, Orr Sharpe, Erik Samayoa, Daisuke Harada, Jan-Renier A J Moonen, Aiqin Cao, Pin-I Chen, Jan K Hennigs, Mingxia Gu, Caiyun G Li, Ryan D Leib, Dan Li, Christopher M Adams, Patricia A Del Rosario, Matthew Bill, Francois Haddad, Jose G Montoya, William H Robinson, Wendy J Fantl, Garry P Nolan, Roham T Zamanian, Mark R Nicolls, Charles Y Chiu, Maria E Ariza, Marlene Rabinovitch,

<h4>Background</h4>Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, ... Read more >>

Circulation (Circulation)
[2017, 136(20):1920-1935]

Cited: 16 times

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Transcriptomic and epigenomic differences in human induced pluripotent stem cells generated from six reprogramming methods.

Jared M Churko, Jaecheol Lee, Mohamed Ameen, Mingxia Gu, Meenakshi Venkatasubramanian, Sebastian Diecke, Karim Sallam, Hogune Im, Gavin Wang, Joseph D Gold, Nathan Salomonis, Michael P Snyder, Joseph C Wu,

Many reprogramming methods can generate human induced pluripotent stem cells (hiPSCs) that closely resemble human embryonic stem cells (hESCs). This has led to assessments of how similar hiPSCs are to hESCs, by evaluating differences in gene expression, epigenetic marks and differentiation potential. However, all previous studies were performed using hiPSCs ... Read more >>

Nat Biomed Eng (Nature biomedical engineering)
[2017, 1(10):826-837]

Cited: 12 times

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Induced Pluripotent Stem Cell Model of Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity.

Silin Sa, Mingxia Gu, James Chappell, Ning-Yi Shao, Mohamed Ameen, Kathryn A T Elliott, Dan Li, Fabian Grubert, Caiyun G Li, Shalina Taylor, Aiqin Cao, Yu Ma, Ryan Fong, Long Nguyen, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

<h4>Rationale</h4>Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies.<h4>Objectives</h4>Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2017, 195(7):930-941]

Cited: 35 times

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Patient-Specific and Genome-Edited Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Brugada Syndrome.

Ping Liang, Karim Sallam, Haodi Wu, Yingxin Li, Ilanit Itzhaki, Priyanka Garg, Ying Zhang, Vittavat Vermglinchan, Feng Lan, Mingxia Gu, Tingyu Gong, Yan Zhuge, Chunjiang He, Antje D Ebert, Veronica Sanchez-Freire, Jared Churko, Shijun Hu, Arun Sharma, Chi Keung Lam, Melvin M Scheinman, Donald M Bers, Joseph C Wu,

<h4>Background</h4>Brugada syndrome (BrS), a disorder associated with characteristic electrocardiogram precordial ST-segment elevation, predisposes afflicted patients to ventricular fibrillation and sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to a lack of adequate human cellular ... Read more >>

J Am Coll Cardiol (Journal of the American College of Cardiology)
[2016, 68(19):2086-2096]

Cited: 77 times

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Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.

Mingxia Gu, Ning-Yi Shao, Silin Sa, Dan Li, Vittavat Termglinchan, Mohamed Ameen, Ioannis Karakikes, Gustavo Sosa, Fabian Grubert, Jaecheol Lee, Aiqin Cao, Shalina Taylor, Yu Ma, Zhixin Zhao, James Chappell, Rizwan Hamid, Eric D Austin, Joseph D Gold, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. Here, we used comparison of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from three families with unaffected mutation carriers (UMCs), FPAH patients, and gender-matched controls ... Read more >>

Cell Stem Cell (Cell stem cell)
[2017, 20(4):490-504.e5]

Cited: 78 times

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Activation of integrin α5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells.

Xiaoli Sun, Yi Fu, Mingxia Gu, Lu Zhang, Dan Li, Hongliang Li, Shu Chien, John Y-J Shyy, Yi Zhu,

Local flow patterns determine the uneven distribution of atherosclerotic lesions. Membrane lipid rafts and integrins are crucial for shear stress-regulated endothelial function. In this study, we investigate the role of lipid rafts and integrin α5 in regulating the inflammatory response in endothelial cells (ECs) under atheroprone versus atheroprotective flow. Lipid ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2016, 113(3):769-774]

Cited: 43 times

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In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug.

Rachel K Hopper, Jan-Renier A J Moonen, Isabel Diebold, Aiqin Cao, Christopher J Rhodes, Nancy F Tojais, Jan K Hennigs, Mingxia Gu, Lingli Wang, Marlene Rabinovitch,

<h4>Background</h4>We previously reported high-throughput RNA sequencing analyses that identified heightened expression of the chromatin architectural factor High Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs) from patients who had idiopathic pulmonary arterial hypertension (PAH) in comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal transition in cancer, we hypothesized ... Read more >>

Circulation (Circulation)
[2016, 133(18):1783-1794]

Cited: 86 times

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RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Christopher J Rhodes, Hogune Im, Aiqin Cao, Jan K Hennigs, Lingli Wang, Silin Sa, Pin-I Chen, Nils P Nickel, Kazuya Miyagawa, Rachel K Hopper, Nancy F Tojais, Caiyun G Li, Mingxia Gu, Edda Spiekerkoetter, Zhaoying Xian, Rui Chen, Mingming Zhao, Mark Kaschwich, Patricia A Del Rosario, Daniel Bernstein, Roham T Zamanian, Joseph C Wu, Michael P Snyder, Marlene Rabinovitch,

RATIONALE:Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. OBJECTIVES:RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess ... Read more >>

Am J Respir Crit Care Med (American journal of respiratory and critical care medicine)
[2015, 192(3):356-366]

Cited: 40 times

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