Darrell N. Kotton

Alveolar and airway progenitors converge on an epigenetically encoded profibrotic state

The paper identifies a conserved profibrotic transitional state arising from alveolar and airway progenitors in fibrosis and shows its epigenetic regulation.

Immunomodulatory RIG-I Agonist SLR14 Confers Protection Against a Range of Highly Pathogenic Negative Sense RNA viruses

SLR14, an immunomodulatory RIG-I agonist, provides broad-spectrum antiviral protection against multiple highly pathogenic negative-sense RNA viruses in vitro and in vivo.

Vessel Organoids Reveal FOXF1 Variant-Specific Regulation of Mesoderm and Capillary Development

The paper uses vessel organoids to study how different FOXF1 variants affect mesoderm and capillary development in humans, showing variant-specific disruptions and potential therapeutic rescue.

Mesothelial Plasticity Specifies a Pleural Immune Circuit that Orchestrates Lung Regeneration

The paper identifies mesothelial cell plasticity as a key determinant of regenerative versus degenerative lung repair by comparing pneumonectomy and chronic lung allograft dysfunction models.

Modeling cell-cell interactions to advance drug discovery in Idiopathic Pulmonary Fibrosis

This study develops a 3D co-culture organoid model of IPF to investigate epithelial-fibroblast interactions and test anti-fibrotic drugs.

A chimeric human-mouse lung vascular model using induced pluripotent stem cells reveals insights into the pathogenesis of BMPR2-related pulmonary hypertension

The paper develops a chimeric human-mouse lung vascular model using hiPSCs to study BMPR2-related pulmonary hypertension, revealing novel molecular and functional defects in human endothelial cells.

The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells

This study shows that PRC2 maintains AT2 cell fate in the adult lung by preventing transitions to ABI and basal-like states, both in vitro and in vivo.

Lentiviral-mediated gene complementation rescues pathogenic ABCA3 variants

This study tests lentiviral-mediated ABCA3 gene complementation in cell lines with specific pathogenic variants, showing partial rescue of cellular functions and differential effects based on variant type.

Divergent Pathways of Surfactant Protein C Maturation for Disease-Associated Isoforms

This study compares the maturation pathways of wild-type and disease-associated SP-C mutants, showing divergent trafficking and processing due to mutations.

Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis

The paper establishes a human iPSC-derived co-culture model of pulmonary fibrosis that reveals bidirectional fibrogenic epithelial-mesenchymal crosstalk and identifies potential druggable pathways.

Impaired AMPK Control of Alveolar Epithelial Cell Metabolism Promotes Pulmonary Fibrosis

The paper identifies impaired AMPK signaling in AT2 cells as a driver of pulmonary fibrosis and shows restoring AMPK alleviates fibrosis in vivo.

Targeted pre-conditioning and cell transplantation in the murine lower respiratory tract

This study demonstrates that targeted pre-conditioning and bronchoscopic cell delivery can effectively regenerate airway epithelium in mice, with transplanted cells differentiating into functional lineages.

Nuclear size-regulated emergence of topological packing order on growing human lung alveolospheres

This study shows that cell packing order in human lung alveolospheres increases with nucleus-to-cell size ratio, resembling a gas-to-liquid transition, and may regulate organ development and maturation.

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels

This study develops a Matrigel-free method using synthetic hydrogels to form alveolar organoids, showing they secrete their own extracellular matrix for growth.

Complex optogenetic spatial patterning with split recombinase

This paper introduces a method to spatially control cell fate using optogenetic recombinase switches and precise illumination, enabling high-resolution patterning of heterogeneous cell populations.

Deciphering Endothelial and Mesenchymal Organ Specification in Vascularized Lung and Intestinal Organoids

This study develops a human pluripotent stem cell-derived organoid system to investigate vascular, mesenchymal, and epithelial co-development in lung and intestinal organoids, revealing organ-specific endothelial and mesenchymal features.

Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme

This study generates lung-specific mesenchyme from mouse iPSCs, identifies key signaling pathways, and demonstrates functional interactions with lung epithelial progenitors.

Learning dynamics by computational integration of single cell genomic and lineage information

This paper introduces CoSpar, a computational method that integrates single-cell genomics with lineage tracing to infer cell dynamics, revealing previously undetected fate biases in hematopoiesis, reprogramming, and differentiation.

Recapitulate Human Cardio-pulmonary Co-development Using Simultaneous Multilineage Differentiation of Pluripotent Stem Cells

This paper develops a method to simultaneously differentiate cardiac and lung epithelial lineages from human pluripotent stem cells to study cardio-pulmonary interactions during embryogenesis.

SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication

Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells

This paper reports the derivation of airway basal stem cells from human iPSCs, demonstrating their ability to self-renew and differentiate into airway epithelial cell types, and model lung diseases.

SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response

This study uses human stem cell-derived alveolar type 2 cells to model SARS-CoV-2 infection, revealing rapid inflammatory responses and drug efficacy against the virus.

A dual mechanism of enhancer activation by FOXA pioneer factors induces endodermal organ fates

The paper shows FOXA pioneer factors prime some enhancers but require lineage-specific TFs to activate others, influencing endodermal organ fate decisions.

Hidden neural states underlie canary song syntax

The paper identifies neurons in canary HVC that encode past song transitions over multiple phrases and seconds, revealing neural mechanisms for syntactic song structure.

Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors

Human iPSC-derived alveolar type II-like and airway epithelial cells adapted to two-dimensional air-liquid interface culture express ACE2 and TMPRSS2 at frequencies comparable to primary lung epithelial controls.

Reconstructed signaling and regulatory networks identify potential drugs for SARS-CoV-2 infection

The paper reconstructs signaling and regulatory networks for SARS-CoV-2 infection and identifies potential drug targets by integrating multi-omics data and experimental validation.

Single-cell time-series mapping of cell fate trajectories reveals an expanded developmental potential for human PSC-derived distal lung progenitors

The paper maps cell fate trajectories of human PSC-derived distal lung progenitors using scRNA-seq and identifies developmental plasticity regulated by Wnt signaling.