ArticlePLoS genetics2013
Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- Integrated multiomic analysis identifies TRIP13 as a mediator of alveolar epithelial type II cell dysfunction in idiopathic pulmonary fibrosis.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Pharmacological expansion of type 2 alveolar epithelial cells promotes regenerative lower airway repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alveolar type I cells can give rise to KRAS-induced lung adenocarcinoma.Cell reports · 2023Article
- Development of human alveolar epithelial cell models to study distal lung biology and disease.iScience · 2022Article
- Article
- Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition.Stem cells (Dayton, Ohio) · 2021Article
- Article
- TENET 2.0: Identification of key transcriptional regulators and enhancers in lung adenocarcinoma.PLoS genetics · 2020Article
- Genome-wide integration of microRNA and transcriptomic profiles of differentiating human alveolar epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration.International journal of molecular sciences · 2020Review
- Article
- Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus InfectionJournal of virology · 2019Article
- CLDN18.1 attenuates malignancy and related signaling pathways of lung adenocarcinoma in vivo and in vitro.International journal of cancer · 2018Article
- Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.Respiratory research · 2018Article
- Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes.Epigenomics · 2018Article
- TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.Cold Spring Harbor perspectives in biology · 2018Review
- Tissue-Specific Control of Tissue-Resident Memory T Cells.Critical reviews in immunology · 2018Review
- TCR-pMHC encounter differentially regulates transcriptomes of tissue-resident CD8 T cells.European journal of immunology · 2018Article
- WNT signaling - lung cancer is no exception.Respiratory research · 2017Review
- Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers.Human molecular genetics · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.