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Wellington V. Cardoso

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https://www.readbyqxmd.com/read/27509163/an-official-american-thoracic-society-workshop-report-2015-stem-cells-and-cell-therapies-in-lung-biology-and-diseases
#1
Darcy E Wagner, Wellington V Cardoso, Sarah E Gilpin, Susan Majka, Harald Ott, Scott H Randell, Bernard Thébaud, Thomas Waddell, Daniel J Weiss
The University of Vermont College of Medicine, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, Cystic Fibrosis Foundation, European Respiratory Society, International Society for Cellular Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 27 to 30, 2015, at the University of Vermont. The conference objectives were to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases...
August 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27463400/erratum-cis-regulatory-architecture-of-a-brain-signaling-center-predates-the-origin-of-chordates
#2
Yao Yao, Paul J Minor, Ying-Tao Zhao, Yongsu Jeong, Ariel M Pani, Anna N King, Orsolya Symmons, Lin Gan, Wellington V Cardoso, François Spitz, Christopher J Lowe, Douglas J Epstein
No abstract text is available yet for this article.
July 27, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27364009/epithelial-notch-signaling-regulates-lung-alveolar-morphogenesis-and-airway-epithelial-integrity
#3
Po-Nien Tsao, Chisa Matsuoka, Shu-Chen Wei, Atsuyasu Sato, Susumu Sato, Koichi Hasegawa, Hung-Kuan Chen, Thai-Yen Ling, Munemasa Mori, Wellington V Cardoso, Mitsuru Morimoto
Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial-mesenchymal interactions that lead to alveolar formation in the developing lung...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27064252/cis-regulatory-architecture-of-a-brain-signaling-center-predates-the-origin-of-chordates
#4
Yao Yao, Paul J Minor, Ying-Tao Zhao, Yongsu Jeong, Ariel M Pani, Anna N King, Orsolya Symmons, Lin Gan, Wellington V Cardoso, François Spitz, Christopher J Lowe, Douglas J Epstein
Genomic approaches have predicted hundreds of thousands of tissue-specific cis-regulatory sequences, but the determinants critical to their function and evolutionary history are mostly unknown. Here we systematically decode a set of brain enhancers active in the zona limitans intrathalamica (zli), a signaling center essential for vertebrate forebrain development via the secreted morphogen Sonic hedgehog (Shh). We apply a de novo motif analysis tool to identify six position-independent sequence motifs together with their cognate transcription factors that are essential for zli enhancer activity and Shh expression in the mouse embryo...
May 2016: Nature Genetics
https://www.readbyqxmd.com/read/26235047/crumbs3-mediated-polarity-directs-airway-epithelial-cell-fate-through-the-hippo-pathway-effector-yap
#5
Aleksander D Szymaniak, John E Mahoney, Wellington V Cardoso, Xaralabos Varelas
Epithelial cells undergo dynamic polarity changes as organs pattern, but the relationship between epithelial polarity and cell fate is poorly understood. Using the developing lung as a model, we found that distinct alterations in apical-basal polarity dictate airway epithelial differentiation. We demonstrate that Crb3, a Crumbs isoform that determines epithelial apical domain identity, is required for airway differentiation by controlling the localization of the transcriptional regulator Yap. We show that Crb3 promotes the interaction between Yap and the Hippo pathway kinases Lats1/2 at apical cell junctions to induce Yap phosphorylation and cytoplasmic retention, which drive cell differentiation...
August 10, 2015: Developmental Cell
https://www.readbyqxmd.com/read/25564622/notch3-jagged-signaling-controls-the-pool-of-undifferentiated-airway-progenitors
#6
Munemasa Mori, John E Mahoney, Maria R Stupnikov, Jesus R Paez-Cortez, Aleksander D Szymaniak, Xaralabos Varelas, Dan B Herrick, James Schwob, Hong Zhang, Wellington V Cardoso
Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation...
January 15, 2015: Development
https://www.readbyqxmd.com/read/25245693/culture-of-mouse-embryonic-foregut-explants
#7
Felicia Chen, Wellington V Cardoso
The ability to culture embryonic organ rudiments and follow their development ex vivo has helped to understand how tissues are constructed and what cellular and biological events are important in this process. Here we outline a technique for isolation and ex vivo growth of foregut explants from E8.5 mouse embryos. This technique serves as a reliable tool for the analysis of the morphogenetic processes and signaling networks during early development of foregut derivatives, such as the lungs.
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/25043473/the-hippo-pathway-effector-yap-controls-patterning-and-differentiation-of-airway-epithelial-progenitors
#8
John E Mahoney, Munemasa Mori, Aleksander D Szymaniak, Xaralabos Varelas, Wellington V Cardoso
How epithelial progenitor cells integrate local signals to balance expansion with differentiation during organogenesis is still little understood. Here, we provide evidence that the Hippo pathway effector Yap is a key regulator of this process in the developing lung. We show that when epithelial tubules are forming and branching, a nucleocytoplasmic shift in Yap localization marks the boundary between the airway and the distal lung compartments. At this transition zone, Yap specifies a transcriptional program that controls Sox2 expression and ultimately generates the airway epithelium...
July 28, 2014: Developmental Cell
https://www.readbyqxmd.com/read/24586412/analysis-of-notch-signaling-dependent-gene-expression-in-developing-airways-reveals-diversity-of-clara-cells
#9
Arjun Guha, Michelle Vasconcelos, Rui Zhao, Adam C Gower, Jayaraj Rajagopal, Wellington V Cardoso
Clara cells (CCs) are a morphologically and operationally heterogeneous population of Secretoglobin Scgb1a1-expressing secretory cells that are crucial for airway homeostasis and post-injury repair. Analysis of the extent and origin of CC diversity are limited by knowledge of genes expressed in these cells and their precursors. To identify novel putative markers of CCs and explore the origins of CC diversity, we characterized global changes in gene expression in embryonic lungs in which CCs do not form due to conditional disruption of Notch signaling (Rbpjk(CNULL))...
2014: PloS One
https://www.readbyqxmd.com/read/24401276/prenatal-retinoid-deficiency-leads-to-airway-hyperresponsiveness-in-adult-mice
#10
Felicia Chen, Hector Marquez, Youn-Kyung Kim, Jun Qian, Fengzhi Shao, Alan Fine, William W Cruikshank, Loredana Quadro, Wellington V Cardoso
There is increasing evidence that vitamin A deficiency in utero correlates with abnormal airway smooth muscle (SM) function in postnatal life. The bioactive vitamin A metabolite retinoic acid (RA) is essential for formation of the lung primordium; however, little is known about the impact of early fetal RA deficiency on postnatal lung structure and function. Here, we provide evidence that during murine lung development, endogenous RA has a key role in restricting the airway SM differentiation program during airway formation...
February 2014: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/23798474/diffuse-lung-disease-in-children-summary-of-a-scientific-conference
#11
Aaron Hamvas, Robin Deterding, William E Balch, David A Schwartz, Kurt H Albertine, Jeffrey A Whitsett, Wellington V Cardoso, Darrell N Kotton, Stella Kourembanas, James S Hagood
A multi-disciplinary scientific conference focused on diffuse and interstitial lung diseases in children was held in La Jolla, CA in June 2012. The conference brought together clinicians (including Pediatric and Adult Pulmonologists, Neonatologists, Pathologists, and Radiologists), clinical researchers, basic scientists, government agency representatives, patient advocates, as well as children affected by diffuse lung disease (DLD) and their families, to review recent scientific developments and emerging concepts in the pathophysiology of childhood DLD...
April 2014: Pediatric Pulmonology
https://www.readbyqxmd.com/read/23607856/molecular-determinants-of-lung-development
#12
REVIEW
Edward E Morrisey, Wellington V Cardoso, Robert H Lane, Marlene Rabinovitch, Steven H Abman, Xingbin Ai, Kurt H Albertine, Richard D Bland, Harold A Chapman, William Checkley, Jonathan A Epstein, Christopher R Kintner, Maya Kumar, Parviz Minoo, Thomas J Mariani, Donald M McDonald, Yoh-Suke Mukouyama, Lawrence S Prince, Jeff Reese, Janet Rossant, Wei Shi, Xin Sun, Zena Werb, Jeffrey A Whitsett, Dorothy Gail, Carol J Blaisdell, Qing S Lin
Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases...
April 2013: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/22797898/neuroepithelial-body-microenvironment-is-a-niche-for-a-distinct-subset-of-clara-like-precursors-in-the-developing-airways
#13
Arjun Guha, Michelle Vasconcelos, Yan Cai, Mitsuhiro Yoneda, Anne Hinds, Jun Qian, Guihua Li, Lauren Dickel, Jane E Johnson, Shioko Kimura, Jinjin Guo, Jill McMahon, Andrew P McMahon, Wellington V Cardoso
Clara cells of mammalian airways have multiple functions and are morphologically heterogeneous. Although Notch signaling is essential for the development of these cells, it is unclear how Notch influences Clara cell specification and if diversity is established among Clara cell precursors. Here we identify expression of the secretoglobin Scgb3a2 and Notch activation as early events in a program of secretory cell fate determination in developing murine airways. We show that Scgb3a2 expression in vivo is Notch-dependent at early stages and ectopically induced by constitutive Notch1 activation, and also that in vitro Notch signaling together with the pan-airway transcription factor Ttf1 (Nkx2...
July 31, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/22651576/maternal-smoking-and-the-retinoid-pathway-in-the-developing-lung
#14
Sara E Manoli, Lacey A Smith, Carrie A Vyhlidal, Chang Hyeok An, Yolanda Porrata, Wellington V Cardoso, Rebecca M Baron, Kathleen J Haley
BACKGROUND: Maternal smoking is a risk factor for pediatric lung disease, including asthma. Animal models suggest that maternal smoking causes defective alveolarization in the offspring. Retinoic acid signaling modulates both lung development and postnatal immune function. Thus, abnormalities in this pathway could mediate maternal smoking effects. We tested whether maternal smoking disrupts retinoic acid pathway expression and functioning in a murine model. METHODS: Female C57Bl/6 mice with/without mainstream cigarette smoke exposure (3 research cigarettes a day, 5 days a week) were mated to nonsmoking males...
2012: Respiratory Research
https://www.readbyqxmd.com/read/22582174/cellular-flice-like-inhibitory-protein-deviates-myofibroblast-fas-induced-apoptosis-toward-proliferation-during-lung-fibrosis
#15
Regina Golan-Gerstl, Shulamit B Wallach-Dayan, Philip Zisman, Wellington V Cardoso, Ronald H Goldstein, Raphael Breuer
A prominent feature of fibrotic tissue in general and of lungs in particular is fibroblast proliferation and accumulation. In patients overcoming fibrosis, apoptosis limits this excessive cell growth. We have previously shown resistance to Fas-induced apoptosis of primary lung fibroblasts from mice with bleomycin-induced lung fibrosis, their escape from immune surveillance, and continued accumulation in spite of overexpression of the Fas death receptor. Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced apoptosis in many cell types...
September 2012: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/22187428/trinucleotide-repeat-containing-6a-tnrc6a-mediated-microrna-function-is-required-for-development-of-yolk-sac-endoderm
#16
Zhihua Jiang, Nan Yu, Pingping Kuang, Melody Chen, Fengzhi Shao, Gregory Martin, David H K Chui, Wellington V Cardoso, Xingbin Ai, Jining Lü
Tnrc6 family members (Tnrc6a/b/c) are key components of the RNA-induced silencing complex in microRNA (miRNA)-mediated gene suppression. Here, we show that Tnrc6a, also known as GW182, is selectively expressed in the yolk sac endoderm and that gene trap disruption of GW182 leads to growth arrest and apoptosis. We found that targets of miRNAs highly expressed in the yolk sac are significantly derepressed in GW182(gt/gt) mutant mice, although levels of miRNAs are not altered. Specifically, growth arrest and apoptosis phenotype are associated with significant derepression of Cdkn1a (p21), Cdkn1c (P27), Lats1, Lats2, Rb1, Rbl, Bim, and Pten, known targets of miRNAs from miR-17/20/93/106 clusters highly expressed in yolk sac endoderm...
February 17, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/21791528/notch-signaling-prevents-mucous-metaplasia-in-mouse-conducting-airways-during-postnatal-development
#17
Po-Nien Tsao, Shu-Chen Wei, Ming-Fang Wu, Miao-Tzu Huang, Hsien-Yi Lin, Ming-Cheng Lee, Kurt Ming-Chao Lin, I-Jong Wang, Vesa Kaartinen, Liang-Tung Yang, Wellington V Cardoso
Goblet cell metaplasia and mucus overproduction contribute to the pathogenesis of chronic lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). Notch signaling regulates cell fate decisions and is crucial in controlling goblet cell differentiation in the gut epithelium. Little is known, however, about how endogenous Notch signaling influences the goblet cell differentiation program that takes place in the postnatal lung. Using a combination of genetic and in vitro approaches here we provide evidence of a novel role for Notch in restricting goblet cell differentiation in the airway epithelium during the postnatal period...
August 2011: Development
https://www.readbyqxmd.com/read/21357686/lacrimal-gland-development-and-fgf10-fgfr2b-signaling-are-controlled-by-2-o-and-6-o-sulfated-heparan-sulfate
#18
Xiuxia Qu, Christian Carbe, Chenqi Tao, Andrea Powers, Roger Lawrence, Toin H van Kuppevelt, Wellington V Cardoso, Kay Grobe, Jeffrey D Esko, Xin Zhang
Heparan sulfate, an extensively sulfated glycosaminoglycan abundant on cell surface proteoglycans, regulates intercellular signaling through its binding to various growth factors and receptors. In the lacrimal gland, branching morphogenesis depends on the interaction of heparan sulfate with Fgf10-Fgfr2b. To address if lacrimal gland development and FGF signaling depends on 2-O-sulfation of uronic acids and 6-O-sulfation of glucosamine residues, we genetically ablated heparan sulfate 2-O and 6-O sulfotransferases (Hs2st, Hs6st1, and Hs6st2) in developing lacrimal gland...
April 22, 2011: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20971881/mir-29-is-a-major-regulator-of-genes-associated-with-pulmonary-fibrosis
#19
Leah Cushing, Ping Ping Kuang, Jun Qian, Fengzhi Shao, Junjie Wu, Frederic Little, Victor J Thannickal, Wellington V Cardoso, Jining Lü
MicroRNAs (miRNA) are small regulatory RNAs that control gene expression by translational suppression and destabilization of target mRNAs. There is increasing evidence that miRNAs regulate genes associated with fibrosis in organs, such as the heart, kidney, liver, and the lung. In a large-scale screening for miRNAs potentially involved in bleomycin-induced fibrosis, we found expression of miR-29 family members significantly reduced in fibrotic lungs. Analysis of normal lungs showed the presence of miR-29 in subsets of interstitial cells of the alveolar wall, pleura, and at the entrance of the alveolar duct, known sites of pulmonary fibrosis...
August 2011: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/20484817/a-retinoic-acid-dependent-network-in-the-foregut-controls-formation-of-the-mouse-lung-primordium
#20
Felicia Chen, Yuxia Cao, Jun Qian, Fengzhi Shao, Karen Niederreither, Wellington V Cardoso
The developmental abnormalities associated with disruption of signaling by retinoic acid (RA), the biologically active form of vitamin A, have been known for decades from studies in animal models and humans. These include defects in the respiratory system, such as lung hypoplasia and agenesis. However, the molecular events controlled by RA that lead to formation of the lung primordium from the primitive foregut remain unclear. Here, we present evidence that endogenous RA acts as a major regulatory signal integrating Wnt and Tgfbeta pathways in the control of Fgf10 expression during induction of the mouse primordial lung...
June 2010: Journal of Clinical Investigation
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