A Novel MIP-1-Expressing Macrophage Subtype in BAL Fluid from Healthy Volunteers

Paul A. Reyfman, Elizabeth S. Malsin, Basil Khuder, Nikita Joshi, Gaurav Gadhvi, Annette S. Flozak, Mary A. Carns, Kathleen Aren, Isaac A. Goldberg, Seokjo Kim, Michael Jason Alexander, Peter H.S. Sporn, Alexander V. Misharin, G. R.Scott Budinger, Ai Phan Lam, Monique E Hinchcliff, Cara J. Gottardi, Deborah Rachelle Winter

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Tissue availability remains an important limitation of single-cell genomic technologies for investigating cellular heterogeneity in human health and disease. BAL represents a minimally invasive approach to assessing an individual's lung cellular environment for diagnosis and research. However, the lack of high-quality, healthy lung reference data is a major obstacle to using single-cell approaches to study a plethora of lung diseases. Here, we performed single-cell RNA sequencing on over 40,000 cells isolated from the BAL of four healthy volunteers. Of the six cell types or lineages we identified, macrophages were consistently the most numerous across individuals. Our analysis confirmed the expression of marker genes defining cell types despite background signals because of the ambient RNA found in many single-cell studies. We assessed the variability of gene expression across macrophages and defined a distinct subpopulation of cells expressing a set of genes associated with Macrophage Inflammatory Protein 1 (MIP-1). RNA in situ hybridization and reanalysis of published lung single-cell data validated the presence of this macrophage subpopulation. Thus, our study characterizes lung macrophage heterogeneity in healthy individuals and provides a valuable resource for future studies to understand the lung environment in health and disease.

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume68
Issue number2
DOIs
StatePublished - Feb 1 2023

Keywords

  • BAL
  • genomics
  • heterogeneity
  • lung immunology
  • macrophage

ASJC Scopus subject areas

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

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