Single-Cell Profiling of Premature Neonate Airways Reveals a Continuum of Myeloid Differentiation

Holly Welfley, Ranjit Kylat, Nahla Zaghloul, Marilyn Halonen, Fernando D. Martinez, Mohamed Ahmed, Darren A. Cusanovich

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Single-cell genomic technologies hold great potential to advance our understanding of lung development and disease. A major limitation lies in accessing intact cells from primary lung tissues for profiling human airway health. Sampling methods such as endotracheal aspiration that are compatible with clinical interventions could enable longitudinal studies, the enrollment of large cohorts, and the development of novel diagnostics. To explore single-cell RNA sequencing profiling of the cell types present at birth in the airway lumen of extremely premature neonates (,28 wk gestation), we isolated cells from endotracheal aspirates collected from intubated neonates within the first hour after birth. We generated data on 10 subjects, providing a rich view of airway luminal biology at a critical developmental period. Our results show that cells present in the airways of premature neonates primarily represent a continuum of myeloid differentiation, including fetal monocytes (25% of total), intermediate myeloid populations (48%), and macrophages (2.6%). Applying trajectory analysis to the myeloid populations, we identified two trajectories consistent with the developmental stages of interstitial and alveolar macrophages, as well as a third trajectory presenting an alternative pathway bridging the distinct macrophage precursors. The three trajectories share many dynamic genes (N = 5,451), but also have distinct transcriptional changes (259 alveolar-specific, 666 interstitial-specific, and 285 bridging-specific). Overall, our results define cells isolated within the so-called “golden hour of birth” in extremely premature neonate airways, representing complex lung biology, and can be used in studies of human development and disease.

Original languageEnglish (US)
Pages (from-to)689-697
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume69
Issue number6
DOIs
StatePublished - Dec 2023

Keywords

  • genomics
  • lung
  • newborn

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Single-Cell Profiling of Premature Neonate Airways Reveals a Continuum of Myeloid Differentiation'. Together they form a unique fingerprint.

Cite this