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Wellington V. Cardoso

Thais de Barros Mendes Lopes, Espen E Groth, Mariana Veras, Tatiane K Furuya, Natalia de Souza Xavier Costa, Gabriel Ribeiro Júnior, Fernanda Degobbi Lopes, Francine M de Almeida, Wellington V Cardoso, Paulo Hilario Nascimento Saldiva, Roger Chammas, Thais Mauad
Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM2.5 (from São Paulo, Brazil; target dose 600 μg/m3 for 1 h daily). Exposure was started on embryonic day 5...
June 4, 2018: Environmental Pollution
Ying Yang, Wellington V Cardoso
Submucosal glands contribute to the luminal secretions of conducting airways in the respiratory tract. In this issue of Cell Stem Cell, both Tata et al. (2018) and Lynch et al. (2018) report that myoepithelial cells of submucosal glands serve as reserve stem cells to regenerate the damaged surface epithelium following severe airway injury.
May 3, 2018: Cell Stem Cell
Ying Yang, Paul Riccio, Michael Schotsaert, Munemasa Mori, Jining Lu, Dong-Kee Lee, Adolfo García-Sastre, Jianming Xu, Wellington V Cardoso
Basal cells (BCs) are p63-expressing multipotent progenitors of skin, tracheoesophageal and urinary tracts. p63 is abundant in developing airways; however, it remains largely unclear how embryonic p63+ cells contribute to the developing and postnatal respiratory tract epithelium, and ultimately how they relate to adult BCs. Using lineage-tracing and functional approaches in vivo, we show that p63+ cells arising from the lung primordium are initially multipotent progenitors of airway and alveolar lineages but later become restricted proximally to generate the tracheal adult stem cell pool...
March 26, 2018: Developmental Cell
Benjamin M Smith, Hussein Traboulsi, John H M Austin, Ani Manichaikul, Eric A Hoffman, Eugene R Bleecker, Wellington V Cardoso, Christopher Cooper, David J Couper, Stephen M Dashnaw, Jia Guo, MeiLan K Han, Nadia N Hansel, Emlyn W Hughes, David R Jacobs, Richard E Kanner, Joel D Kaufman, Eric Kleerup, Ching-Long Lin, Kiang Liu, Christian M Lo Cascio, Fernando J Martinez, Jennifer N Nguyen, Martin R Prince, Stephen Rennard, Stephen S Rich, Leora Simon, Yanping Sun, Karol E Watson, Prescott G Woodruff, Carolyn J Baglole, R Graham Barr
Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts ( n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Munemasa Mori, Renin Hazan, Paul S Danielian, John E Mahoney, Huijun Li, Jining Lu, Emily S Miller, Xueliang Zhu, Jacqueline A Lees, Wellington V Cardoso
Abnormal development of multiciliated cells is a hallmark of a variety of human conditions associated with chronic airway diseases, hydrocephalus and infertility. Multiciliogenesis requires both activation of a specialized transcriptional program and assembly of cytoplasmic structures for large-scale centriole amplification that generates basal bodies. It remains unclear, however, what mechanism initiates formation of these multiprotein complexes in epithelial progenitors. Here we show that this is triggered by nucleocytoplasmic translocation of the transcription factor E2f4...
July 4, 2017: Nature Communications
Maria R Stupnikov, Wellington V Cardoso
Neuroendocrine cells act as oxygen sensors in animals from fish to humans, but the evolutionary origins of these cells are only just becoming clear.
May 19, 2017: ELife
Arjun Guha, Aditya Deshpande, Aradhya Jain, Paola Sebastiani, Wellington V Cardoso
There is evidence that certain club cells (CCs) in the murine airways associated with neuroepithelial bodies (NEBs) and terminal bronchioles are resistant to the xenobiotic naphthalene (Nap) and repopulate the airways after Nap injury. The identity and significance of these progenitors (variant CCs, v-CCs) have remained elusive. A recent screen for CC markers identified rare Uroplakin3a (Upk3a)-expressing cells (U-CCs) with a v-CC-like distribution. Here, we employ lineage analysis in the uninjured and chemically injured lungs to investigate the role of U-CCs as epithelial progenitors...
April 11, 2017: Cell Reports
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
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
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
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
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
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
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
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
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
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
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
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
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
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