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Human Primary Airway Basal Cells Display a Continuum of Molecular Phases from Health to Disease in Chronic Obstructive Pulmonary Disease

Wijk, Sofia C LU ; Prabhala, Pavan LU ; Michaliková, Barbora LU ; Sommarin, Mikael LU ; Doyle, Alexander LU ; Lang, Stefan LU orcid ; Kanzenbach, Karina LU ; Tufvesson, Ellen LU ; Lindstedt, Sandra LU and Leigh, Nicholas D LU orcid , et al. (2021) In American Journal of Respiratory Cell and Molecular Biology 65(1). p.103-113
Abstract

Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to Chronic Obstructive Pulmonary Disease (COPD) and other lung disorders. In order to reveal how basal cells contribute to disease, and to discover novel therapeutic targets, these basal cells need to be further characterized. In this study, we optimized a flow cytometry-based cell sorting protocol for primary human airway basal cells dependent on cell size and Nerve-Growth Factor Receptor (NGFR) expression. The basal cell population was found to be molecularly and functionally heterogeneous in contrast to cultured basal cells. In addition, significant differences were found such as KRT14 expression... (More)

Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to Chronic Obstructive Pulmonary Disease (COPD) and other lung disorders. In order to reveal how basal cells contribute to disease, and to discover novel therapeutic targets, these basal cells need to be further characterized. In this study, we optimized a flow cytometry-based cell sorting protocol for primary human airway basal cells dependent on cell size and Nerve-Growth Factor Receptor (NGFR) expression. The basal cell population was found to be molecularly and functionally heterogeneous in contrast to cultured basal cells. In addition, significant differences were found such as KRT14 expression exclusively existing in cultured cells. Also, colony-forming capacity was significantly increased in cultured cells showing a clonal enrichment in vitro. Next, by single cell RNA sequencing on primary basal cells from healthy donors and GOLD stage IV COPD patients, the gene expression revealed a continuum ranging from healthy basal cell signatures to diseased basal cell phenotypes. We identified several upregulated genes that may indicate COPD, such as stress response related genes GADD45B and AHSA1, along with genes involved in the response to hypoxia such as CITED2 and SOD1. Taken together, the presence of healthy basal cells in stage IV COPD demonstrates the potential for regeneration through the discovery of novel therapeutic targets. In addition, we show the importance of studying primary basal cells when investigating disease mechanisms as well as for developing future cell-based therapies in the human lung.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Respiratory Cell and Molecular Biology
volume
65
issue
1
pages
103 - 113
publisher
American Thoracic Society
external identifiers
  • scopus:85110298365
  • pmid:33789072
ISSN
1535-4989
DOI
10.1165/rcmb.2020-0464OC
language
English
LU publication?
yes
id
2a06e3bd-80ec-4385-8fee-e3cdc27d6aee
date added to LUP
2021-04-23 10:16:06
date last changed
2024-04-06 02:45:33
@article{2a06e3bd-80ec-4385-8fee-e3cdc27d6aee,
  abstract     = {{<p>Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to Chronic Obstructive Pulmonary Disease (COPD) and other lung disorders. In order to reveal how basal cells contribute to disease, and to discover novel therapeutic targets, these basal cells need to be further characterized. In this study, we optimized a flow cytometry-based cell sorting protocol for primary human airway basal cells dependent on cell size and Nerve-Growth Factor Receptor (NGFR) expression. The basal cell population was found to be molecularly and functionally heterogeneous in contrast to cultured basal cells. In addition, significant differences were found such as KRT14 expression exclusively existing in cultured cells. Also, colony-forming capacity was significantly increased in cultured cells showing a clonal enrichment in vitro. Next, by single cell RNA sequencing on primary basal cells from healthy donors and GOLD stage IV COPD patients, the gene expression revealed a continuum ranging from healthy basal cell signatures to diseased basal cell phenotypes. We identified several upregulated genes that may indicate COPD, such as stress response related genes GADD45B and AHSA1, along with genes involved in the response to hypoxia such as CITED2 and SOD1. Taken together, the presence of healthy basal cells in stage IV COPD demonstrates the potential for regeneration through the discovery of novel therapeutic targets. In addition, we show the importance of studying primary basal cells when investigating disease mechanisms as well as for developing future cell-based therapies in the human lung.</p>}},
  author       = {{Wijk, Sofia C and Prabhala, Pavan and Michaliková, Barbora and Sommarin, Mikael and Doyle, Alexander and Lang, Stefan and Kanzenbach, Karina and Tufvesson, Ellen and Lindstedt, Sandra and Leigh, Nicholas D and Karlsson, Göran and Bjermer, Leif and Westergren Thorsson, Gunilla and Magnusson, Mattias}},
  issn         = {{1535-4989}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  pages        = {{103--113}},
  publisher    = {{American Thoracic Society}},
  series       = {{American Journal of Respiratory Cell and Molecular Biology}},
  title        = {{Human Primary Airway Basal Cells Display a Continuum of Molecular Phases from Health to Disease in Chronic Obstructive Pulmonary Disease}},
  url          = {{http://dx.doi.org/10.1165/rcmb.2020-0464OC}},
  doi          = {{10.1165/rcmb.2020-0464OC}},
  volume       = {{65}},
  year         = {{2021}},
}