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Updated: Jan 7, 2026
Experimental Model to Evaluate Resolution of Pneumonia
Published on: February 17, 2023
Multi-omics analysis reveals distinct spatial compartmentalization of lung repair niches in pediatric ARDS
Licheng Song1, Yaru Liu1, Ying Bai1
1Senior Department of Respiratory and Critical Care Medicine, the Eighth Medical Center of PLA General Hospital, Beijing, 100094, China.
Insights
Children with pediatric acute respiratory distress syndrome (PARDS) show better lung repair than adults due to distinct cellular mechanisms. This study identifies key repair pathways, including KRT17-positive cells and preserved AT2 differentiation, offering insights into age-specific recovery.
Area of Science:
- Pulmonology and critical care medicine
- Pediatric respiratory diseases
- Multi-omics and systems biology
Background:
- Pediatric acute respiratory distress syndrome (PARDS) has higher survival and better lung repair than adult ARDS.
- Mechanisms behind this age-specific advantage in PARDS are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying superior lung repair in pediatric acute respiratory distress syndrome (PARDS).
- To compare pediatric PARDS lung repair pathways with adult lethal COVID-19 lung injury.
- To identify potential therapeutic targets for improving PARDS outcomes.
Main Methods:
- Pilot multi-omics study integrating single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and plasma proteomics in influenza-associated PARDS.
- Harmonization with the Human Lung Cell Atlas (HLCA) and reanalysis of public pediatric PARDS data.
- Comparative analysis with adult lethal COVID-19 lung single-cell data.
Main Results:
- Survivors exhibited spatially restricted repair with preserved alveolar type II (AT2) cells and KRT17 expression, unlike fatal cases and adults.
- Fatal cases and adults showed diffuse immune activation, pro-fibrotic, and pro-apoptotic signaling.
- KRT17-positive airway epithelial cells and resident-like macrophages were associated with recovery, while CTHRC1-enriched fibroblasts correlated with worse outcomes.
Conclusions:
- Putative pediatric lung repair niches in PARDS involve KRT17-positive transitional epithelium, AT2 cell differentiation, and macrophage restoration.
- Diffuse immune activation and specific fibroblast programs may predict poorer outcomes in PARDS.
- HLCA-guided analysis suggests age-related differences in lung repair, necessitating larger studies.
Abstract:
BACKGROUND: Pediatric acute respiratory distress syndrome (PARDS), often triggered by viral infections, is a life-threatening condition. Despite its severity, children demonstrate significantly better survival rates and superior lung repair compared to adults. However, the mechanisms underlying this age-specific advantage remain incompletely understood. PATIENTS AND METHODS: We conducted a pilot multi-omics study of influenza-associated PARDS integrating single-cell RNA sequencing (scRNA-seq) of pediatric lung tissue and bronchoalveolar lavage fluid (BALF), spatial transcriptomics, and plasma proteomics. Analyses were harmonized with the Human Lung Cell Atlas (HLCA) reference, reanalysis of public pediatric PARDS airway scRNA-seq, and contextual comparisons to adult lethal COVID-19 lung. RESULTS: Tissue scRNA-seq and spatial data indicated outcome-linked divergence in PARDS. Survivor showed spatially restricted repair with preserved alveolar type II (AT2) cells, AT2-to-alveolar type I (AT1) differentiation signatures, and higher KRT17, whereas fatal case and adults exhibited diffuse immune activation with pro-fibrotic and pro-apoptotic signaling. In BALF, KRT17-positive airway stress–repair epithelial cells (hillock-like) increased from the acute to recovery phase, and plasma proteomics showed higher circulating KRT17 in survivors. HLCA-based label transfer strengthened cell-type definitions and enabled pediatric–adult comparisons suggesting biological and developmental differences; the adult lethal COVID-19 atlas provided a benchmark with attenuated epithelial repair and prominent collagen CTHRC1-pathologic fibroblasts. Fibroblast programs were regionally compartmentalized, with injury-enriched CTHRC1+ states versus alveolar fibroblasts in preserved areas, and showed stronger injury–homeostasis anti-correlation in fatalities. Myeloid remodeling included BALF transitions from FCN1-high inflammatory states toward FABP4-positive resident-like states, consistent with public pediatric datasets showing reduced inflammatory and interferon-stimulated gene (ISG) modules and severity-linked increases in aged neutrophils. CONCLUSIONS: This pilot multi-omics case series outlines putative pediatric lung repair niches in influenza-associated PARDS. KRT17-positive transitional epithelium, preserved AT2 differentiation, and restoration of resident-like macrophages may align with recovery, whereas diffuse immune activation and CTHRC1-enriched fibroblast programs may accompany worse outcomes. HLCA-guided annotations and adult benchmarks indicate possible age-related differences, warranting validation in larger multi-center cohorts.
