Progenitor identification and SARS-CoV-2 infection in human distal lung organoids.
Nature
; 588(7839): 670-675, 2020 12.
Artículo
en Inglés
| MEDLINE | ID: covidwho-943910
Preprint
Este artículo de revista científica es probablemente basado en un preprint previamente disponible, por medio del reconocimiento de similitud realizado por una máquina. La confirmación humana aún está pendiente.
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Este artículo de revista científica es probablemente basado en un preprint previamente disponible, por medio del reconocimiento de similitud realizado por una máquina. La confirmación humana aún está pendiente.
Ver preprint
ABSTRACT
The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate the investigation of pathologies such as interstitial lung disease, cancer and coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we describe the development of a long-term feeder-free, chemically defined culture system for distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids were able to differentiate into AT1 cells, and basal cell organoids developed lumens lined with differentiated club and ciliated cells. Single-cell analysis of KRT5+ cells in basal organoids revealed a distinct population of ITGA6+ITGB4+ mitotic cells, whose offspring further segregated into a TNFRSF12Ahi subfraction that comprised about ten per cent of KRT5+ basal cells. This subpopulation formed clusters within terminal bronchioles and exhibited enriched clonogenic organoid growth activity. We created distal lung organoids with apical-out polarity to present ACE2 on the exposed external surface, facilitating infection of AT2 and basal cultures with SARS-CoV-2 and identifying club cells as a target population. This long-term, feeder-free culture of human distal lung organoids, coupled with single-cell analysis, identifies functional heterogeneity among basal cells and establishes a facile in vitro organoid model of human distal lung infections, including COVID-19-associated pneumonia.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Organoides
/
Técnicas de Cultivo de Tejidos
/
SARS-CoV-2
/
COVID-19
/
Pulmón
/
Modelos Biológicos
Límite:
Humanos
Idioma:
Inglés
Revista:
Nature
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
S41586-020-3014-1
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