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      LungMAP: The Molecular Atlas of Lung Development Program

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          Abstract

          The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website ( www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users.

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          Most cited references20

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          SINCERA: A Pipeline for Single-Cell RNA-Seq Profiling Analysis

          A major challenge in developmental biology is to understand the genetic and cellular processes/programs driving organ formation and differentiation of the diverse cell types that comprise the embryo. While recent studies using single cell transcriptome analysis illustrate the power to measure and understand cellular heterogeneity in complex biological systems, processing large amounts of RNA-seq data from heterogeneous cell populations creates the need for readily accessible tools for the analysis of single-cell RNA-seq (scRNA-seq) profiles. The present study presents a generally applicable analytic pipeline (SINCERA: a computational pipeline for SINgle CEll RNA-seq profiling Analysis) for processing scRNA-seq data from a whole organ or sorted cells. The pipeline supports the analysis for: 1) the distinction and identification of major cell types; 2) the identification of cell type specific gene signatures; and 3) the determination of driving forces of given cell types. We applied this pipeline to the RNA-seq analysis of single cells isolated from embryonic mouse lung at E16.5. Through the pipeline analysis, we distinguished major cell types of fetal mouse lung, including epithelial, endothelial, smooth muscle, pericyte, and fibroblast-like cell types, and identified cell type specific gene signatures, bioprocesses, and key regulators. SINCERA is implemented in R, licensed under the GNU General Public License v3, and freely available from CCHMC PBGE website, https://research.cchmc.org/pbge/sincera.html.
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            Transcriptional control of lung morphogenesis.

            The vertebrate lung consists of multiple cell types that are derived primarily from endodermal and mesodermal compartments of the early embryo. The process of pulmonary organogenesis requires the generation of precise signaling centers that are linked to transcriptional programs that, in turn, regulate cell numbers, differentiation, and behavior, as branching morphogenesis and alveolarization proceed. This review summarizes knowledge regarding the expression and proposed roles of transcription factors influencing lung formation and function with particular focus on knowledge derived from the study of the mouse. A group of transcription factors active in the endodermally derived cells of the developing lung tubules, including thyroid transcription factor-1 (TTF-1), beta-catenin, Forkhead orthologs (FOX), GATA, SOX, and ETS family members are required for normal lung morphogenesis and function. In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop. Lung formation is dependent on reciprocal signaling among cells of both endodermal and mesenchymal compartments that instruct transcriptional processes mediating lung formation and adaptation to breathing after birth.
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              An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy.

              There is growing recognition and understanding of the entities that cause interstitial lung disease (ILD) in infants. These entities are distinct from those that cause ILD in older children and adults. A multidisciplinary panel was convened to develop evidence-based guidelines on the classification, diagnosis, and management of ILD in children, focusing on neonates and infants under 2 years of age. Recommendations were formulated using a systematic approach. Outcomes considered important included the accuracy of the diagnostic evaluation, complications of delayed or incorrect diagnosis, psychosocial complications affecting the patient's or family's quality of life, and death. No controlled clinical trials were identified. Therefore, observational evidence and clinical experience informed judgments. These guidelines: (1) describe the clinical characteristics of neonates and infants (<2 yr of age) with diffuse lung disease (DLD); (2) list the common causes of DLD that should be eliminated during the evaluation of neonates and infants with DLD; (3) recommend methods for further clinical investigation of the remaining infants, who are regarded as having "childhood ILD syndrome"; (4) describe a new pathologic classification scheme of DLD in infants; (5) outline supportive and continuing care; and (6) suggest areas for future research. After common causes of DLD are excluded, neonates and infants with childhood ILD syndrome should be evaluated by a knowledgeable subspecialist. The evaluation may include echocardiography, controlled ventilation high-resolution computed tomography, infant pulmonary function testing, bronchoscopy with bronchoalveolar lavage, genetic testing, and/or lung biopsy. Preventive care, family education, and support are essential.
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                Author and article information

                Journal
                Am J Physiol Lung Cell Mol Physiol
                Am. J. Physiol. Lung Cell Mol. Physiol
                ajplung
                ajplung
                AJPLUNG
                American Journal of Physiology - Lung Cellular and Molecular Physiology
                American Physiological Society (Bethesda, MD )
                1040-0605
                1522-1504
                1 November 2017
                10 August 2017
                10 August 2017
                : 313
                : 5
                : L733-L740
                Affiliations
                [1] 1RTI International, Research Triangle Park, North Carolina;
                [2] 2Pacific Northwest National Laboratory , Richland, Washington;
                [3] 3Texas Advanced Computing Center , Austin, Texas;
                [4] 4University of Washington , Seattle, Washington;
                [5] 5University of California , San Diego, California;
                [6] 6Yale School of Medicine , New Haven, Connecticut;
                [7] 7University of Rochester Medical Center , Rochester, New York;
                [8] 8Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio;
                [9] 9Children’s Hospital of Los Angeles , Los Angeles, California;
                [10] 10Duke University School of Medicine , Durham, North Carolina; and
                [11] 11University of Alabama , Birmingham, Alabama
                Author notes
                Address for reprint requests and other correspondence: R. F. Clark, RTI International, 3040 East Cornwallis Rd., Research Triangle Park, NC 27709 (e-mail: rclark@ 123456rti.org ).
                Article
                L-00139-2017 L-00139-2017
                10.1152/ajplung.00139.2017
                5792185
                28798251
                1502999a-e1b3-4798-b09a-e013eb0ad997
                Copyright © 2017 the American Physiological Society

                Licensed under Creative Commons Attribution CC-BY 4.0: © the American Physiological Society.

                History
                : 27 March 2017
                : 4 August 2017
                : 7 August 2017
                Funding
                Funded by: http://doi.org/10.13039/100000050 HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)
                Award ID: U01HL122638
                Award ID: U01HL122642
                Award ID: U01HL122700
                Award ID: U01HL122626
                Award ID: U01HL122703
                Award ID: U01HL122681
                Categories
                Review
                Translational Physiology

                Anatomy & Physiology
                lung development,web resource,lung imaging,lung omics,3d imaging,single cell analysis

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