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Accession Number:
AD1064064
Title:
Macrophage Responses to Epithelial Dysfunction Promote Lung Fibrosis in Aging
Corporate Author:
Northwestern University Evanston United States
Report Date:
2018-10-01
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.
Descriptive Note:
Technical Report,30 Sep 2017,29 Sep 2018
Pages:
0018
Distribution Statement:
Approved For Public Release;
File Size:
0.23MB
