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Article

Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis

1
Universities of Giessen and Marburg Lung Center (UGMLC), The German Center for Lung Research (DZL), 35392 Giessen, Germany
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Excellence Cluster Cardiopulmonary Institute (CPI), 35392 Giessen, Germany
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Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
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Institute for Lung Health (ILH), 35392 Giessen, Germany
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Department of Clinical Immunology and Transfusion Medicine, 35392 Giessen, Germany
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Department of General and Thoracic Surgery, University Hospital Giessen, 35392 Giessen, Germany
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Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria
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European IPF Registry/UGLMC Giessen Biobank, 35392 Giessen, Germany
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Lung Clinic Waldhof-Elgershausen, 35753 Greifenstein, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: C Arnold Spek
Cells 2022, 11(2), 235; https://doi.org/10.3390/cells11020235
Received: 30 November 2021 / Revised: 26 December 2021 / Accepted: 4 January 2022 / Published: 11 January 2022
(This article belongs to the Special Issue State of the Art in Idiopathic Pulmonary Fibrosis)
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates, in a reactive manner, all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by LysoTracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial LysoTracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s that behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expressed AEC2 and basal cell markers, resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of LysoTracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5, and CD24 expression in human lung epithelial cells. Combining functional analysis with extracellular and intracellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis. View Full-Text
Keywords: IPF; alveolar epithelial cells; intermediate epithelial cells; transitional states; LysoTracker; flow cytometry; lung transcriptomic profile; CK5; NGFR; CD24 IPF; alveolar epithelial cells; intermediate epithelial cells; transitional states; LysoTracker; flow cytometry; lung transcriptomic profile; CK5; NGFR; CD24
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MDPI and ACS Style

Wasnick, R.M.; Shalashova, I.; Wilhelm, J.; Khadim, A.; Schmidt, N.; Hackstein, H.; Hecker, A.; Hoetzenecker, K.; Seeger, W.; Bellusci, S.; El Agha, E.; Ruppert, C.; Guenther, A. Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis. Cells 2022, 11, 235. https://doi.org/10.3390/cells11020235

AMA Style

Wasnick RM, Shalashova I, Wilhelm J, Khadim A, Schmidt N, Hackstein H, Hecker A, Hoetzenecker K, Seeger W, Bellusci S, El Agha E, Ruppert C, Guenther A. Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis. Cells. 2022; 11(2):235. https://doi.org/10.3390/cells11020235

Chicago/Turabian Style

Wasnick, Roxana Maria, Irina Shalashova, Jochen Wilhelm, Ali Khadim, Nicolai Schmidt, Holger Hackstein, Andreas Hecker, Konrad Hoetzenecker, Werner Seeger, Saverio Bellusci, Elie El Agha, Clemens Ruppert, and Andreas Guenther. 2022. "Differential LysoTracker Uptake Defines Two Populations of Distal Epithelial Cells in Idiopathic Pulmonary Fibrosis" Cells 11, no. 2: 235. https://doi.org/10.3390/cells11020235

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