Biology subjects

Kropski, J. A.

Publications and source records attributed to Kropski, J. A..

At least 19 recordsLinked to original sources

bioRxiv2026

A 4D GelMA-Cad/Gelatin Hydrogel for High-Resolution DMD Bioprinting of Vascularized Soft Tissue Models

Digital micromirror device (DMD)-based bioprinting enables high-resolution fabrication of hydrogel-based tissue constructs, but print fidelity and hydrogel mechanics are typically coupled through polymer concentration, light exposure, and crosslinking density. This creates a materials constraint for vascular bioprinting, where constructs must preserve microscale architecture during fabrication while supporting multicellular remodeling, lumen formation, and long-term tissue organization. To meet these requirements, we developed a 4D GelMA-Cad/gelatin hydrogel with time-dependent mechanics that maintains print fidelity while providing a soft, cell-permissive matrix. GelMA-Cad provides a covalently photocrosslinked, bioactive network containing an N-cadherin-mimetic peptide, while uncrosslinked gelatin serves as a transient matrix-modifying component that diffuses from the hydrogel after fabrication, producing further softening without bulk degradation of the GelMA-Cad network. We characterized hydrogel chemistry with NMR, quantified time-dependent changes in stiffness, visualized pore morphology with cryo-SEM, and evaluated the platform in retinal and pulmonary constructs. The 4D hydrogel supports 3D-patterned accuracy, cell viability, inner blood-retinal barrier vasculature, and vascularized lung-alveolar tissue models. Single-cell RNA-sequencing of the pulmonary vascular-alveolar model demonstrated compartment-specific transcriptional responses, including enrichment of lung capillary-associated endothelial features and AT1-like epithelial states. Overall, this platform decouples DMD print fidelity from post-print matrix mechanics for vascularized soft tissue bioprinting and tissue modeling.

bioengineering↗

bioRxiv2026

IPF distal lung epithelial cells acquire a DNA methylation signature consistent with activation of basal cell transcriptional programs

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease associated with failed alveolar epithelial repair with an expansion of aberrant airway-like epithelium in the alveolar space leading to lung function decline usually resulting in death within 3-5 years of diagnosis. While single-cell and spatial transcriptomic approaches have been used to characterize disease-emergent cell populations, less is known about the regulation of transcriptional programs that drive failed alveolar epithelial cell repair in IPF. DNA methylation is a fundamental layer of gene regulation that stabilizes differentiated cell identity; however, changes in methylation in the epithelial compartment in IPF have not been studied. To identify novel epigenetic mediators of epithelial cell dysfunction, we performed high-resolution DNA methylation profiling of purified distal lung epithelial cells from 10 age-matched control and 14 IPF lungs using Oxford Nanopore Technologies (ONT) whole-genome, long-read sequencing. We identified widespread methylome remodeling in the IPF lung epithelium, with 84% of differentially methylated regions (DMRs) hypomethylated. DMRs were largely found outside of promoters, with 88% outside of 3 kb from the transcription start site (TSS), consistent with altered distal regulatory element activity. DMRs were enriched for transcription factor (TF) binding site motifs and gene associations consistent with dysregulation of polycomb repressive complex 2 (PRC2) and increases in p63 activity. DNA methylation at DMRs associated with p63 target genes, including KRT5, and genes implicated in failed epithelial repair, including MUC5B, MMP7, and S100A2 inversely correlated with gene expression. Consistent with the observed dysregulation of the IPF epithelial methylome, an experimental co-culture model of alveolar type II epithelial cell (AT2s) to basal-like epithelial cell transdifferentiation revealed widespread hypomethylation. Further, sites associated with NKX2.1 and FOXA1/2 binding, TFs involved in alveolar fate maintenance, were hypermethylated, suggesting loss of epigenetic regulation of alveolar identity. Together, these data implicate DNA methylation in the failed alveolar epithelial repair processes in IPF, potentially providing future therapeutic strategies by identifying putative regulatory elements associated with aberrant transcriptional programs.

molecular biology↗

bioRxiv2026

Inflammatory Fibroblasts Promote Repair After Injury Through Epithelial Proliferation

Fibroblast heterogeneity after lung injury is a well observed phenomenon made highly relevant by the widespread application of single cell RNA-sequencing. The characterization of homeostatic and injury associated states has led to the identification of a population of fibroblasts that emerge during inflammation and express cytokines that may potentially amplify the inflammatory circuit. However, whether these cells actively contribute to inflammation or serve an alternative function within the broader injury-repair cascade remains unclear. By integrating several robust murine lung injury data sets we establish the persistence of the inflammatory fibroblast across multiple injury models and identify a role for these cells in lung repair after injury through effects on alveolar epithelial proliferation. We validate this observation in-vivo using a genetic model of spontaneous lung fibrosis and in-vitro with mixed alveolar organoid cultures of various homeostatic and injury associated fibroblasts wherein we identify a mesenchymal-epithelial BMP signaling axis as a key driver of the AT2 cell injury repair response. Finally, we present supporting evidence from human disease, reinforcing the relevance of this fibroblast subset in pathological settings. These findings extend critical observations made prior to the single-cell era and contribute to our evolving understanding of fibroblast heterogeneity as a key feature of lung repair.

molecular biology↗

bioRxiv2026

Fishing with Two Lines: A Hybrid Approach to Spatial Transcriptomic Discovery

Spatial transcriptomics faces a trade-off between the number of genes assayed and depth of per-gene sensitivity. We developed a dual chemistry method that combines the high sensitivity of a 10X Genomics Xenium V1 custom panel (up to 480 genes) with the broad coverage of the Prime 5K panel (5001 genes) on a single tissue section. This involved co-hybridizing Prime and V1 probes and sequentially running the V1 and Prime decoding chemistries. Applied to a human lung tissue microarray, we observed high concordance between the V1 and Prime chemistries when run independently (on serial sections) and the dual chemistry runs. Overlapping genes (profiled on both V1 and Prime chemistries) showed similar expression patterns in the dual run demonstrating the fidelity of the assay. By combining information from both the V1 and Prime chemistries within the same cell, we retain more cells, gain valuable additional information, and enable both high sensitivity profiling and discovery.

molecular biology↗

bioRxiv2025

T-cell Multiomic Analysis Identifies Subsets and Mechanisms of Interaction with Epithelial Cells in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and respiratory failure, with a median survival of 3-5 years. While T-cell numbers are elevated in IPF lungs, their contributions to fibrosis beyond inflammation remain poorly understood. Here, we performed multiplex imaging and single-cell RNA and protein profiling on [~]90,000 CD3 T-cells from control and fibrotic lungs, revealing eleven distinct subsets of CD4 and CD8 T-cells. Among these, we identified a rare CD56 regulatory T-cell subset that is highly activated in fibrosis and exhibits a sustained immunosuppressive phenotype. CXCR4/MIF signaling emerged as a central axis mediating T-cell-epithelial interactions, while epidermal growth factor receptor (EGFR) and TGF{beta} pathways dominated in multiple T-cell subsets. Our findings demonstrate that T-cells in IPF adopt nonclassical activation patterns, driven by epithelial interactions and the fibrotic microenvironment. These studies provide a foundation for exploring novel therapeutic strategies in IPF lungs by modulating T-cell behavior and communication networks.

immunology↗

bioRxiv2025

Denoising image-based spatial transcriptomics data with DenoIST

Image-based spatial transcriptomics (IST) technologies provide unprecedented resolution of gene expression in tissue sections, but suffer from contamination of cells gene expression profiles due to imperfect cell segmentation. We present DenoIST (Denoising Image-based Spatial Transcriptomics data), a new computational tool that accurately identifies and removes contaminating transcripts from IST datasets. DenoIST models the observed transcript counts using a Poisson mixture model that explicitly accounts for local neighbourhood contamination. Applied to multiple real IST datasets of varying cell densities, DenoIST restores gene expression specificity and clarifies local biological structures by identifying and filtering transcripts spilt over from neighbouring cells. The denoised data enable more consistent and interpretable cell type annotation by minimising conflicting gene expression profiles, reducing the prevalence of hybrid or ambiguous cell types, and enhancing the contrast between distinct functional compartments. Overall, we demonstrate that DenoIST can be integrated to existing IST analysis workflows to improve biological interpretability and robustness of IST data.

bioinformatics↗

bioRxiv2025

AlveolEye: Rapid and precise lung morphometry guided by computer vision

Rigorous and reproducible evaluation of lung tissue under different conditions is necessary to interpret development, injury, and pharmacologic interventions. Common histological measurements in the distal lung include mean linear intercept (MLI) as a metric of alveolarization and airspace volume density (ASVD) as a metric of airspaces relative to tissue. Historically, these have been performed manually in a time-intensive process, with reproducible trends, but a high degree of variability between individuals. To improve the reproducibility and throughput of lung morphometry, we developed AlveolEye, an open source, semi-automated, computer vision-assisted tool that rapidly and reproducibly calculates MLI and ASVD from images of standard hematoxylin and eosin (H&E) stained tissue sections. AlveolEye-assisted MLI calculation closely aligns with manually-derived measurements for corresponding images, with preservation of trends in measurements between non-injured controls and neonatal mice subjected to two different injury models. Analyzing human tissue of varying ages suggests that the approach developed in AlveolEye is generalizable across species. Notably, AlveolEye markedly reduced the average variation across individual analyzers, with the greatest improvement in precision among individuals with the least experience in performing lung morphometry. The design of AlveolEye is intentionally semi-automated, preserving the investigators ability to assess and adjust parameters based on sample characteristics. AlveolEye facilitates efficient lung morphological measurements on larger sample sizes, allowing for greater statistical power for preclinical studies, and improves precision across individual observers, allowing for improved rigor in experimental design and execution.

developmental biology↗

bioRxiv2025

Loss of Regulator of telomere elongation helicase (Rtel1) impairs alveolar epithelial cell progenitor function but does not exacerbate experimental fibrosis

Inherited loss-of-function mutations in the replication-associated helicase Regulator of telomere elongation helicase (RTEL1) are among the most frequent monogenic causes of familial pulmonary fibrosis (FPF), but the specific functional role of RTEL1 in lung development, homeostasis, and injury-repair has not been determined. Using single-cell RNA-sequencing to define the cellular diversity and molecular programs following intratracheal bleomycin injury in mice, we observed that Rtel1 was most highly expressed in the lung epithelium, and its expression was reduced in PF epithelial cells compared to nonfibrotic controls. While global deletion of Rtel1 leads to embryonic lethality, constitutive deletion of Rtel1 in the lung epithelium (Rtel{Delta}epi) led to normal lung structure and architecture. Rtel1{Delta}epi mice exhibited accelerated telomere attrition and impaired AEC progenitor potential ex-vivo. Despite decreased AEC progenitor function, no differences in lung fibrosis were observed in Rtel{Delta}epi mice compared to controls following single-dose or repetitive intratracheal bleomycin. Together, these data implicate RTEL1 as a regulator of AEC progenitor function but this level of progenitor dysfunction is not alone sufficient to cause or exacerbate experimental lung fibrosis.

cell biology↗

bioRxiv2025

Sustained Yap/Taz activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling

YAP/TAZ signaling is required for initiation of lung alveolar repair, yet previous studies in idiopathic pulmonary fibrosis (IPF) predicted increased YAP/TAZ signaling in alveolar epithelial cells (AECs). We investigated whether persistent YAP/TAZ AEC signaling contributes to failed epithelial repair and persistent fibrotic remodeling. In IPF lungs, we identified increased YAP+/TAZ+ AECs and increased expression of YAP/TAZ transcriptional targets compared to donor control lungs. In human lung organoids, pharmacological YAP/TAZ activation resulted in phenotype shifts of AECs into aberrant transitional states. In mice with Yap/Taz activation (YTactive) resulting from deletion of Hippo-kinases Stk3/4 in alveolar-type 2 (AT2) cells, resulted in persistent fibrotic remodeling at 28- and 56-days post-bleomycin injury. Gene promoter activity associated with transitional cell markers (Krt19, Hopx, and Runx2) was increased in YTactive AT2 cells. Immunofluorescent staining showed a loss of AT2 associated Cebpa and increased Krt19 in YTactive lineage traced AT2 cells 28 days post-injury. Inhibition of Yap/Taz using Verteporfin resulted in improved lung repair in YTactive mouse lungs, including increased Cebpa and decreased Krt19+ transitional cells. These findings demonstrate sustained Yap/Taz activation drives abnormal alveolar repair and persistent fibrotic remodeling. Blocking aberrant persistent Yap/Taz activity promotes adaptive repair and has potential as a therapeutic strategy for PF.

molecular biology↗

bioRxiv2025

A spatial transcriptomic atlas of acute neonatal lung injury across development and disease severity

A molecular understanding of lung organogenesis requires delineation of the timing and regulation of the cellular transitions that ultimately form and support a surface capable of gas exchange. While the advent of single-cell transcriptomics has allowed for the discovery and identification of transcriptionally distinct cell populations present during lung development, the spatiotemporal dynamics of these transcriptional shifts remain undefined. With imaging-based spatial transcriptomics, we analyzed the gene expression patterns in 17 human infant lungs at varying stages of development and injury, creating a spatial transcriptomic atlas of [~]1.2 million cells. We applied computational clustering approaches to identify shared molecular patterns among this cohort, informing how tissue architecture and molecular spatial relationships are coordinated during development and disrupted in disease. Recognizing that all preterm birth represents an injury to the developing lung, we created a simplified classification scheme that relies upon the routinely collected objective measures of gestational age and life span. Within this framework, we have identified cell type patterns across gestational age and life span variables that would likely be overlooked when using the conventional "disease vs. control" binary comparison. Together, these data represent an open resource for the lung research community, supporting discovery-based inquiry and identification of targetable molecular mechanisms in both normal and arrested human lung development.

genomics↗

bioRxiv2025

SpatialRNA: a Python package for easy application of Graph Neural Network models on single-molecule spatial transcriptomicsdataset

Image-based spatial transcriptomics deliver gene expression measurements of RNA transcripts in tissue slices with single-molecule resolution and spatial context preserved. Modern Graph Neural Network (GNN) models are promising methods for capturing the complex molecular and cellular phenotypes in tissues at single-transcript and single-cell levels. A key application of GNNs is the detection of spatial domains or niches, that is, groups of molecules and/or cells that collaboratively work together to produce complex phenotypes. Due to the vast number of detected transcripts in image-based spatial transcriptomics, applying GNNs on RNA molecule graphs is not trivial. We present a Python package, SpatialRNA, for easy (sub)graph generation from tissue samples and provide comprehensive tutorials for convenient and efficient application of Graph Neural Network models under the PyG framework. Availability and implementation: The SpatialRNA package is freely accessible from GitLab https://gitlab.svi.edu.au/biocellgen-public/spatialrna and can be installed via pip. Python notebooks and scripts used in case studies are freely accessible at https://gitlab.svi.edu.au/biocellgen-public/case_study_ipf and https://gitlab.svi.edu.au/biocellgen-public/case_study_xenium_5k_panel.

bioinformatics↗

bioRxiv2024

Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression

Lung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To examine cellular and molecular dynamics driving evolving BPD in humans, we performed single-cell RNA sequencing of preterm infant lungs in early stages of BPD and BPD+PH compared to term infants. Analysis of the endothelium revealed a unique aberrant capillary cell-state primarily in BPD+PH marked by ANKRD1 expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factor FOXF1 within the alveolar parenchyma in neonatal lung samples with BPD/BPD+PH. Loss of semaphorin signaling was replicated in a murine BPD model and in humans with alveolar capillary dysplasia (ACDMPV), suggesting a mechanistic link between the developmental programs underlying BPD and ACDMPV and a critical role for semaphorin signaling in normal lung development.

genomics↗

bioRxiv2024

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity

Background Pulmonary fibrosis (PF) is a rare lung disease with diverse pathogenesis and multiple interconnected underlying biological mechanisms. Mosaic loss of chromosome Y (mLOY) is one of the most common forms of acquired chromosome abnormality in men, which has been reported to be associated with increased risk of various chronic progressive diseases including fibrotic diseases. However, the exact role of mLOY in the development of PF remains elusive and to be elucidated. MethodsWe adopted three complementary approaches to explore the role of mLOY in the pathogenesis of PF. We used copy number on chromosome Y to estimate mLOY comparing patients in PROFILE and gnomAD cohorts and between cases and control patients from the GE100KGP cohort. Correlation of mLOY with demographic and clinical variables was tested using patients from PROFILE cohort. Lung single-cell transcriptomic data were analysed to assess the cell types implicated in mLOY. We performed Mendelian randomisation to examine the causal relationship between mLOY, IPF, and telomere length. ResultsThe genetic analysis suggests that mLOY is found in PF from both case cohorts but when compared with an age matched population the effect is minimal (P = 0.0032). mLOY is related to age (P = 0.00021) and shorter telomere length (P = 0.0081) rather than PF severity or progression. Single-cell analysis indicates that mLOY appears to be found primarily in immune cells and appears to be related to presence and severity of fibrosis. Mendelian randomisation demonstrates that mLOY is not on the causal pathway for IPF, but partial evidence supports that telomere shortening is on the causal pathway for mLOY. ConclusionOur study confirms the existence of mLOY in PF patients and suggests that mLOY is not a major driver of IPF. The combined evidence suggests a triangulation model where telomere shortening leads to both IPF and mLOY.

genomics↗

bioRxiv2023

Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis

The human lung is structurally complex, with a diversity of specialized epithelial, stromal and immune cells playing specific functional roles in anatomically distinct locations, and large-scale changes in the structure and cellular makeup of this distal lung is a hallmark of pulmonary fibrosis (PF) and other progressive chronic lung diseases. Single-cell transcriptomic studies have revealed numerous disease-emergent/enriched cell types/states in PF lungs, but the spatial contexts wherein these cells contribute to disease pathogenesis has remained uncertain. Using sub-cellular resolution image-based spatial transcriptomics, we analyzed the gene expression of more than 1 million cells from 19 unique lungs. Through complementary cell-based and innovative cell-agnostic analyses, we characterized the localization of PF-emergent cell-types, established the cellular and molecular basis of classical PF histopathologic disease features, and identified a diversity of distinct molecularly-defined spatial niches in control and PF lungs. Using machine-learning and trajectory analysis methods to segment and rank airspaces on a gradient from normal to most severely remodeled, we identified a sequence of compositional and molecular changes that associate with progressive distal lung pathology, beginning with alveolar epithelial dysregulation and culminating with changes in macrophage polarization. Together, these results provide a unique, spatially-resolved characterization of the cellular and molecular programs of PF and control lungs, provide new insights into the heterogeneous pathobiology of PF, and establish analytical approaches which should be broadly applicable to other imaging-based spatial transcriptomic studies.

genomics↗

bioRxiv2023

Hypoxia-inducible factor-2 (HIF2) regulates alveolar regeneration after repetitive injury

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and often fatal chronic respiratory disease thought to result from repetitive injury and failed repair of the lung alveoli, and recent studies have identified a number of disease-emergent intermediate/transitional cell states in the IPF lung supporting this concept. In this study, we found that persistent activation of hypoxia-inducible factor (HIF)-signaling in airway-derived, repair-associated cell types/states is a hallmark of dysfunctional epithelial repair in the IPF lung epithelium and experimental models of recurrent lung epithelial injury. Disrupting Hif-signaling attenuated experimental lung fibrosis, reduced mucous-secretory cell polarization, and promoted functional alveolar regeneration following repetitive injury. Mouse and human organoid studies demonstrated that small-molecule-based HIF2 inhibition promoted alveolar epithelial cell proliferation and maturation while preventing the emergence of maladaptive intermediate/transitional states analogous to those in IPF. Together, these studies indicate that targeted HIF2-inhibition represents a novel and effective therapeutic strategy to promote functional lung regeneration, and could be readily translated into human studies of IPF and other chronic interstitial lung diseases with disease modifying effect. One sentence summaryInhibiting hypoxia-inducible-factor 2 (HIF2) promotes functional lung alveolar epithelial repair following recurrent injury.

cell biology↗

bioRxiv2023

Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ have been implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrate that Yap and Taz are normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2 to AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to a LPS injury prevented AT1 cell regeneration, led to intra-alveolar collagen deposition, and resulted in persistent innate inflammation. Together these findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

cell biology↗

bioRxiv2023

Myeloid Cell-Derived IL1β Contributes to Pulmonary Vascular Remodeling in Heart Failure with Preserved Ejection Fraction

BackgroundPulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are not well understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH in HFpEF, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. MethodsEight week old male and female C57/BL6J mice were given either L-NAME and high fat diet (HFD) or control water/diet for 2,5, and 12 weeks. Bulk RNA sequencing and single cell RNA sequencing was performed to identify early and cell-specific pathways that might regulate pulmonary vascular remodeling in PH-HFpEF. Finally, clodronate liposome and IL1{beta} antibody treatments were utilized to deplete macrophages or IL1{beta}, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF. ResultsMice given L-NAME/HFD developed PH, small vessel muscularization, and right heart dysfunction after 2 weeks of treatment. Inflammation-related gene ontologies were over-represented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling of mouse lung and plasma showed an increase in IL1{beta}, which was confirmed in plasma from patients with HFpEF. Single cell sequencing of mouse lungs also showed an increase in M1-like, pro-inflammatory populations of Ccr2+ monocytes and macrophages, and transcript expression of IL1{beta} was primarily restricted to myeloid-type cells. Finally, clodronate liposome treatment prevented the development of PH in L-NAME/HFD treated mice, and IL1{beta} antibody treatment also attenuated PH in L-NAME/HFD treated mice. ConclusionsOur study demonstrated that a well-accepted model of HFpEF recapitulates features of pulmonary vascular remodeling commonly seen in patients with HFpEF, and we identified myeloid cell derived IL1{beta} as an important contributor to PH in HFpEF.

cell biology↗

bioRxiv2023

Cell type-specific and disease-associated eQTL in the human lung

Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis (PF). Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA-sequencing of lung tissue from 67 PF and 49 unaffected donors. Employing a pseudo-bulk approach, we mapped expression quantitative trait loci (eQTL) across 38 cell types, observing both shared and cell type-specific regulatory effects. Further, we identified disease-interaction eQTL and demonstrated that this class of associations is more likely to be cell-type specific and linked to cellular dysregulation in PF. Finally, we connected PF risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression, and implicates context-specific eQTL as key regulators of lung homeostasis and disease.

genomics↗