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Meta-Analysis of COVID-19 BAL Single-Cell RNA Sequencing Reveals Alveolar Epithelial Transitions and Unique Alveolar Epithelial Cell Fates.
Karmaus, Peer W F; Tata, Aleksandra; Meacham, Julie M; Day, Frank; Thrower, David; Tata, Purushothama Rao; Fessler, Michael B.
Afiliação
  • Karmaus PWF; Immunity, Inflammation, and Disease Laboratory and.
  • Tata A; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina.
  • Meacham JM; Immunity, Inflammation, and Disease Laboratory and.
  • Day F; Office of Scientific Computing, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and.
  • Thrower D; Office of Scientific Computing, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and.
  • Tata PR; Department of Cell Biology, School of Medicine, Duke University, Durham, North Carolina.
  • Fessler MB; Immunity, Inflammation, and Disease Laboratory and.
Am J Respir Cell Mol Biol ; 69(6): 623-637, 2023 12.
Article em En | MEDLINE | ID: mdl-37523502
Single-cell RNA sequencing (scRNA-seq) of BAL cells has provided insights into coronavirus disease (COVID-19). However, reports have been limited by small patient cohorts. We performed a meta-analysis of BAL scRNA-seq data from healthy control subjects (n = 13) and patients with COVID-19 (n = 20), sourced from six independent studies (167,280 high-quality cells in total). Consistent with the source reports, increases in infiltrating leukocyte subtypes were noted, several with type I IFN signatures and unique gene expression signatures associated with transcellular chemokine signaling. Noting dramatic reductions of inferred NKX2-1 and NR4A1 activity in alveolar epithelial type II (AT-II) cells, we modeled pseudotemporal AT-II-to-AT-I progression. This revealed changes in inferred AT-II cell metabolic activity, increased transitional cells, and a previously undescribed AT-I state. This cell state was conspicuously marked by the induction of genes of the epidermal differentiation complex, including the cornified envelope protein SPRR3 (small proline-rich protein 3), upregulation of multiple KRT (keratin) genes, inferred mitochondrial dysfunction, and cell death signatures including apoptosis and ferroptosis. Immunohistochemistry of lungs from patients with COVID-19 confirmed upregulation and colocalization of KRT13 and SPRR3 in the distal airspaces. Forced overexpression of SPRR3 in human alveolar epithelial cells ex vivo did not activate caspase-3 or upregulate KRT13, suggesting that SPRR3 marks an AT-I cornification program in COVID-19 but is not sufficient for phenotypic changes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Epiteliais Alveolares / COVID-19 Tipo de estudo: Systematic_reviews Limite: Humans Idioma: En Revista: Am J Respir Cell Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Epiteliais Alveolares / COVID-19 Tipo de estudo: Systematic_reviews Limite: Humans Idioma: En Revista: Am J Respir Cell Mol Biol Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article