Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nature 2020 ; 588 (7839): 670-675 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Progenitor identification and SARS-CoV-2 infection in human distal lung organoids #MMPMID33238290
Salahudeen AA; Choi SS; Rustagi A; Zhu J; van Unen V; de la O SM; Flynn RA; Margalef-Catala M; Santos AJM; Ju J; Batish A; Usui T; Zheng GXY; Edwards CE; Wagar LE; Luca V; Anchang B; Nagendran M; Nguyen K; Hart DJ; Terry JM; Belgrader P; Ziraldo SB; Mikkelsen TS; Harbury PB; Glenn JS; Garcia KC; Davis MM; Baric RS; Sabatti C; Amieva MR; Blish CA; Desai TJ; Kuo CJ
Nature 2020[Dec]; 588 (7839): 670-675 PMID33238290show ga
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 TNFRSF12A(hi) 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.