Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection

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 scann...

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Main Authors: Yin, Lu, Chen, Jianzhu, Xu, Shuoyu, Cheng, Jierong, Zheng, Dahai, Limmon, Gino V., Leung, Nicola H. N., Rajapakse, Jagath C., Chow, Vincent T. K., Yu, Hanry
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: SPIE 2013
Online Access:http://hdl.handle.net/1721.1/80344
https://orcid.org/0000-0002-5687-6154
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author Yin, Lu
Chen, Jianzhu
Xu, Shuoyu
Cheng, Jierong
Zheng, Dahai
Limmon, Gino V.
Leung, Nicola H. N.
Rajapakse, Jagath C.
Chow, Vincent T. K.
Yu, Hanry
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Yin, Lu
Chen, Jianzhu
Xu, Shuoyu
Cheng, Jierong
Zheng, Dahai
Limmon, Gino V.
Leung, Nicola H. N.
Rajapakse, Jagath C.
Chow, Vincent T. K.
Yu, Hanry
author_sort Yin, Lu
collection MIT
description 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[superscript +] to Scgb1a1[superscript −]. 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.
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spelling mit-1721.1/803442022-09-28T13:52:00Z Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection Yin, Lu Chen, Jianzhu Xu, Shuoyu Cheng, Jierong Zheng, Dahai Limmon, Gino V. Leung, Nicola H. N. Rajapakse, Jagath C. Chow, Vincent T. K. Yu, Hanry Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu 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[superscript +] to Scgb1a1[superscript −]. 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. Janssen Pharmaceutical Ltd. (Grant R-185-000-182-592) Janssen Pharmaceutical Ltd. (Grant R-185-000-228-592) Singapore-MIT Alliance for Research and Technology Center. 2013-09-03T16:03:20Z 2013-09-03T16:03:20Z 2013-04 2013-03 Article http://purl.org/eprint/type/JournalArticle 1083-3668 1560-2281 http://hdl.handle.net/1721.1/80344 Yin, Lu. “Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection.” Journal of Biomedical Optics 18, no. 4 (April 1, 2013): 046001. https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1117/1.JBO.18.4.046001 Journal of Biomedical Optics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf SPIE SPIE
spellingShingle Yin, Lu
Chen, Jianzhu
Xu, Shuoyu
Cheng, Jierong
Zheng, Dahai
Limmon, Gino V.
Leung, Nicola H. N.
Rajapakse, Jagath C.
Chow, Vincent T. K.
Yu, Hanry
Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title_full Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title_fullStr Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title_full_unstemmed Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title_short Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
title_sort spatiotemporal quantification of cell dynamics in the lung following influenza virus infection
url http://hdl.handle.net/1721.1/80344
https://orcid.org/0000-0002-5687-6154
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