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Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury

Alveolar epithelial cells (AECs) play a role in chemically induced acute lung injury (CALI). However, the mechanisms that induce alveolar epithelial type 2 cells (AEC2s) to proliferate, exit the cell cycle, and transdifferentiate into alveolar epithelial type 1 cells (AEC1s) are unclear. Here, we in...

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Autores principales: Cao, Chao, Memete, Obulkasim, Shao, Yiru, Zhang, Lin, Liu, Fuli, Dun, Yu, He, Daikun, Zhou, Jian, Shen, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820093/
https://www.ncbi.nlm.nih.gov/pubmed/36613719
http://dx.doi.org/10.3390/ijms24010277
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author Cao, Chao
Memete, Obulkasim
Shao, Yiru
Zhang, Lin
Liu, Fuli
Dun, Yu
He, Daikun
Zhou, Jian
Shen, Jie
author_facet Cao, Chao
Memete, Obulkasim
Shao, Yiru
Zhang, Lin
Liu, Fuli
Dun, Yu
He, Daikun
Zhou, Jian
Shen, Jie
author_sort Cao, Chao
collection PubMed
description Alveolar epithelial cells (AECs) play a role in chemically induced acute lung injury (CALI). However, the mechanisms that induce alveolar epithelial type 2 cells (AEC2s) to proliferate, exit the cell cycle, and transdifferentiate into alveolar epithelial type 1 cells (AEC1s) are unclear. Here, we investigated the epithelial cell types and states in a phosgene-induced CALI rat model. Single-cell RNA-sequencing of bronchoalveolar lavage fluid (BALF) samples from phosgene-induced CALI rat models (Gas) and normal controls (NC) was performed. From the NC and Gas BALF samples, 37,245 and 29,853 high-quality cells were extracted, respectively. All cell types and states were identified and divided into 23 clusters; three cell types were identified: macrophages, epithelial cells, and macrophage proliferating cells. From NC and Gas samples, 1315 and 1756 epithelial cells were extracted, respectively, and divided into 11 clusters. The number of AEC1s decreased considerably following phosgene inhalation. A unique SOX9-positive AEC2 cell type that expanded considerably in the CALI state was identified. This progenitor cell type may develop into alveolar cells, indicating its stem cell differentiation potential. We present a single-cell genome-scale transcription map that can help uncover disease-associated cytologic signatures for understanding biological changes and regeneration of lung tissues during CALI.
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spelling pubmed-98200932023-01-07 Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury Cao, Chao Memete, Obulkasim Shao, Yiru Zhang, Lin Liu, Fuli Dun, Yu He, Daikun Zhou, Jian Shen, Jie Int J Mol Sci Article Alveolar epithelial cells (AECs) play a role in chemically induced acute lung injury (CALI). However, the mechanisms that induce alveolar epithelial type 2 cells (AEC2s) to proliferate, exit the cell cycle, and transdifferentiate into alveolar epithelial type 1 cells (AEC1s) are unclear. Here, we investigated the epithelial cell types and states in a phosgene-induced CALI rat model. Single-cell RNA-sequencing of bronchoalveolar lavage fluid (BALF) samples from phosgene-induced CALI rat models (Gas) and normal controls (NC) was performed. From the NC and Gas BALF samples, 37,245 and 29,853 high-quality cells were extracted, respectively. All cell types and states were identified and divided into 23 clusters; three cell types were identified: macrophages, epithelial cells, and macrophage proliferating cells. From NC and Gas samples, 1315 and 1756 epithelial cells were extracted, respectively, and divided into 11 clusters. The number of AEC1s decreased considerably following phosgene inhalation. A unique SOX9-positive AEC2 cell type that expanded considerably in the CALI state was identified. This progenitor cell type may develop into alveolar cells, indicating its stem cell differentiation potential. We present a single-cell genome-scale transcription map that can help uncover disease-associated cytologic signatures for understanding biological changes and regeneration of lung tissues during CALI. MDPI 2022-12-23 /pmc/articles/PMC9820093/ /pubmed/36613719 http://dx.doi.org/10.3390/ijms24010277 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cao, Chao
Memete, Obulkasim
Shao, Yiru
Zhang, Lin
Liu, Fuli
Dun, Yu
He, Daikun
Zhou, Jian
Shen, Jie
Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title_full Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title_fullStr Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title_full_unstemmed Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title_short Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
title_sort single-cell rna-sequencing reveals epithelial cell signature of multiple subtypes in chemically induced acute lung injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820093/
https://www.ncbi.nlm.nih.gov/pubmed/36613719
http://dx.doi.org/10.3390/ijms24010277
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