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Updated: Jul 24, 2025
Droplet Barcoding-Based Single Cell Transcriptomics of Adult Mammalian Tissues
Published on: January 10, 2019
Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome
Tim Flerlage1,2, Jeremy Chase Crawford3, E Kaitlynn Allen3
1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
Insights
Pediatric ARDS involves immune responses. This study found reduced interferon gene expression and altered immune cell programs in severe cases, suggesting new therapeutic targets for acute respiratory failure in infants.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Genomics
Background:
- Acute respiratory distress syndrome (ARDS) in children, or pediatric ARDS (pARDS), is a severe condition linked to abnormal immune responses.
- Understanding the immune mechanisms in pARDS is crucial for developing effective treatments.
Purpose of the Study:
- To investigate microbial and host gene expression profiles in tracheal aspirates from infants with acute respiratory failure.
- To identify immune signatures associated with the severity of pediatric ARDS.
Main Methods:
- Longitudinal collection of tracheal aspirates from infants with acute respiratory failure.
- Microbial sequencing and single-cell gene expression analysis.
- Comparison of transcriptional profiles between moderate-to-severe pARDS and mild/no pARDS groups.
Main Results:
- Reduced interferon-stimulated gene (ISG) expression was observed in moderate to severe pARDS.
- Altered transcriptional programs in mononuclear phagocytes (MNPs) and progressive airway neutrophilia were identified.
- Folate Receptor 3 (FOLR3), an innate immune cell product, was enriched in moderate to severe pARDS.
- Distinct inflammatory profiles correlated with pARDS etiology and severity, particularly in RSV-induced cases.
Conclusions:
- Reduced ISG expression, altered macrophage repair programs, and aged neutrophil accumulation are implicated in moderate to severe pARDS pathogenesis.
- Immune responses in pARDS are diverse and depend on the cause and severity.
- Findings highlight potential biomarkers and therapeutic targets for pARDS.
Abstract:
Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.
