Open Access
1 April 2013 Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
Lu Yin, Shuoyu Xu, Jierong Cheng, Dahai Zheng, Gino V. Limmon, Nicola H. Leung, Jagath Rajapakse, Vincent T. K. Chow, Jianzhu Chen, Hanry Yu
Author Affiliations +
Funded by: Singapore-MIT Alliance for Research and Technology’s Infectious Disease Interdisciplinary Research Group, Institute of Bioengineering and Nanotechnology, Biomedical Research Counciland, Institute of Bioengineering and Nanotechnology, Biomedical Research Council, A*STAR; grants from Janssen, Singapore-MIT Alliance Computational and Systems Biology Flagship Project, SMART BioSyM and Mechanobiology Institute of Singapore, Mechanobiology Institute
Abstract
Lung injury caused by influenza virus infection is widespread. Understanding lung damage and repair progression post infection requires quantitative spatiotemporal information on various cell types mapping into the tissue structure. Based on high content images acquired from an automatic slide scanner, we have developed algorithms to quantify cell infiltration in the lung, loss and recovery of Clara cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing bronchiolar epithelial cells (SBECs). These quantitative analyses reveal: prolonged immune cell infiltration into the lung that persisted long after the influenza virus was cleared and paralleled with Clara cell recovery; more rapid loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs from Scgb1a1 + to Scgb1a1 . These results provide evidence supporting a new mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC intermediates and shed light on the understanding of the lung damage and repair process. The approach and algorithms in quantifying cell-level changes in the tissue context (cell-based tissue informatics) to gain mechanistic insights into the damage and repair process can be expanded and adapted in studying other disease models.
CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Lu Yin, Shuoyu Xu, Jierong Cheng, Dahai Zheng, Gino V. Limmon, Nicola H. Leung, Jagath Rajapakse, Vincent T. K. Chow, Jianzhu Chen, and Hanry Yu "Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection," Journal of Biomedical Optics 18(4), 046001 (1 April 2013). https://doi.org/10.1117/1.JBO.18.4.046001
Published: 1 April 2013
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CITATIONS
Cited by 16 scholarly publications.
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KEYWORDS
Lung

Tissues

Algorithm development

Image segmentation

Injuries

Medical research

Scanners

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