ArticleBMC genomics2021
Comprehensive epigenomic profiling of human alveolar epithelial differentiation identifies key epigenetic states and transcription factor co-regulatory networks for maintenance of distal lung identity.
Article in BMC genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- A temporal single cell atlas of dynamic chromatin accessibility during murine lung maturation.Nature communications · 2026Article
- Single-cell eQTL mapping reveals cell-type-specific genetic regulation in lung cancer.Cell genomics · 2026Article
- The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells.bioRxiv : the preprint server for biology · 2026Article
- Single-nucleus multi-omics delineates distinct epigenetic programs associated with tumor progression in lung adenocarcinoma.Clinical epigenetics · 2026Article
- PRMT5 inhibitors actively promote metastatic progression of lung adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- A Multimodal Spatial and Epigenomic Atlas of Human Adult Lung Topography.bioRxiv : the preprint server for biology · 2025Article
- Integrative analysis of gene expression and chromatin dynamics multi-omics data in mouse models of bleomycin-induced lung fibrosis.Epigenetics & chromatin · 2025Article
- 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
- Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.JCI insight · 2024Article
- Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity.The European respiratory journal · 2023Article
- Motif and conserved module analysis in DNA (promoters, enhancers) and RNA (lncRNA, mRNA) using AlModules.Scientific reports · 2022Article
- FOXO1 Couples KGF and PI-3K/AKT Signaling to NKX2.1-Regulated Differentiation of Alveolar Epithelial Cells.Cells · 2022Article
- A single-cell regulatory map of postnatal lung alveologenesis in humans and mice.Cell genomics · 2022Article
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15 authors at 2 institutions in 1 country.
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Abstract
backgroundDisruption of alveolar epithelial cell (AEC) differentiation is implicated in distal lung diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung adenocarcinoma that impact morbidity and mortality worldwide. Elucidating underlying disease pathogenesis requires a mechanistic molecular understanding of AEC differentiation. Previous studies have focused on changes of individual transcription factors, and to date no study has comprehensively characterized the dynamic, global epigenomic alterations that facilitate this critical differentiation process in humans.
resultsWe comprehensively profiled the epigenomic states of human AECs during type 2 to type 1-like cell differentiation, including the methylome and chromatin functional domains, and integrated this with transcriptome-wide RNA expression data. Enhancer regions were drastically altered during AEC differentiation. Transcription factor binding analysis within enhancer regions revealed diverse interactive networks with enrichment for many transcription factors, including NKX2-1 and FOXA family members, as well as transcription factors with less well characterized roles in AEC differentiation, such as members of the MEF2, TEAD, and AP1 families. Additionally, associations among transcription factors changed during differentiation, implicating a complex network of heterotrimeric complex switching in driving differentiation. Integration of AEC enhancer states with the catalog of enhancer elements in the Roadmap Epigenomics Mapping Consortium and Encyclopedia of DNA Elements (ENCODE) revealed that AECs have similar epigenomic structures to other profiled epithelial cell types, including human mammary epithelial cells (HMECs), with NKX2-1 serving as a distinguishing feature of distal lung differentiation.
conclusionsEnhancer regions are hotspots of epigenomic alteration that regulate AEC differentiation. Furthermore, the differentiation process is regulated by dynamic networks of transcription factors acting in concert, rather than individually. These findings provide a roadmap for understanding the relationship between disruption of the epigenetic state during AEC differentiation and development of lung diseases that may be therapeutically amenable.
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