Accession Number:

AD1064064

Title:

Macrophage Responses to Epithelial Dysfunction Promote Lung Fibrosis in Aging

Descriptive Note:

Technical Report,30 Sep 2017,29 Sep 2018

Corporate Author:

Northwestern University Evanston United States

Personal Author(s):

• Misharin, Alexander

Report Date:

2018-10-01

Pagination or Media Count:

18.0

Abstract:

Aim 1 and 2 Using mouse models of lung injury, fibrosis and epithelial dysfunction, we have demonstrated that microenvironment is a key factor driving phenotype of profibrotic alveolar macrophages. We have shown that epithelial dysfunction promotes recruitment of monocyte-derived alveolar macrophages and leads to exaggerated pulmonary fibrosis. Aim 3. Pulmonary fibrosis is a heterogeneous syndrome in which fibrotic scar replaces normal lung tissue. We performed massively parallel single-cell RNA-Seq on lung tissue from eight lung transplant donors and eight patients with pulmonary fibrosis. Combined with in situ RNA hybridization, with amplification, these data provide a molecular atlas of disease pathobiology. We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to non-overlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. Analysis of a cryobiopsy specimen from a patient with early disease supports the clinical application of single-cell RNA-Seq to develop personalized approaches to therapy.

Descriptors:

• macrophages
• alveoli
• lung diseases
• FIBROSIS
• BIOLOGICAL AGING
• models
• pathology
• RNA SEQUENCE ANALYSIS
• ribonucleic acids
• epithelial cells
• gene expression
• hybridization

Subject Categories:

• Medicine and Medical Research
• Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE