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| Status |
Public on Nov 03, 2016 |
| Title |
Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. In this study, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes. Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as highly specific to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells and is not expressed in bronchial epithelial cells, while RT-PCR confirmed that it is not expressed in endothelial cells. Utilizing GRAMD2 as a new AT1 cell-specific gene will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.
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| Overall design |
Two preps of purified AT1 cells (92%, and 93% pure, respectively) were isolated from Sprague-Dawley male rats and RNA was extracted using Trizol. In addition, RNA was extracted from bronchoalveolar lavage cells and 14 rat tissues: kidney, spleen, ileum, duodenum, colon, stomach, skin, brain, testis, skeletal muscle, trachea, heart, salivary gland, and liver.
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| Contributor(s) |
Marconett CN, Zhou B, Sunohara M, Pouldar TM, Wang H, Liu Y, Rieger ME, Tran E, Flodby P, Siegmund KD, Crandall ED, Laird-Offringa IA, Borok Z |
| Citation(s) |
27749084 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL114094 |
Epigenetic profiling of human alveolar epithelial cells in health and disease |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Borok, ITE A LAIRD-OFFRINGA |
| R37 HL062569 |
Molecular programming of AEC differentiation: role of forkhead factors |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Borok |
| R01 HL112638 |
Mechanisms of beta-catenin signaling in alveolar epithelial cell differentiation |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Borok, Kahn |
| R01 HL114959 |
Epithelial abnormalities in IPF: role of ER stress and GRP78/BiP |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Zhou |
| U01 HL108634 |
MAPGen Knowledge Base (MAPGenKB) and Coordination Center |
UNIVERSITY OF SOUTHERN CALIFORNIA |
EDWARD DAVID CRANDALL, XIANGHONG Jasmine ZHOU |
| R01 HL126877 |
Role of claudin 18 in regulation of lung stem/progenitor cell homeostasis |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Borok |
| P30 CA014089 |
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORT |
UNIVERSITY OF SOUTHERN CALIFORNIA |
PETER A JONES |
| P30 DK048522 |
USC RESEARCH CENTER FOR LIVER DISEASES: USC CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC RESEARCH CENTER FOR LIVER DISEASES: USC Research Center for Liver Disease: USC RESEARCH CENTER FOR LIVER DISEASES: USC Research Center for Liver Disease: USC Research Center for Liver Disease: USC Research Center for Liver Disease: USC Research Center for Liver Disease: USC Research Center for Liver Disease |
UNIVERSITY OF SOUTHERN CALIFORNIA |
KAPLOWITZ |
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| Submission date |
Jul 07, 2014 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Crystal N Marconett |
| E-mail(s) |
cmarcone@usc.edu, cmarconett@coh.org
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| Phone |
626-218-4357
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| Organization name |
City of Hope
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| Department |
Integrative Translational Sciences
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| Lab |
Crystal Marconett
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| Street address |
1500 E Duarte Rd
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL6101 |
Illumina ratRef-12 v1.0 expression beadchip |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA254464 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE59120_RAW.tar |
2.8 Mb |
(http)(custom) |
TAR |
| GSE59120_non_normalized.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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