Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Authors: Abo et al.

Link to paper: https://doi.org/10.1101/2020.06.03.132639

Journal/ Pre-Print: bioRxiv

Tags: Cell Biology, Gut, Stem cells

Research Highlights

1. Comparison of RNA seq data of key alveolar epithelial type 2 (AT2) genes from primary human adult AT2s and induced pluripotent stem cell (iPSC) derived AT2 (iAT2s) with 150 lung cancer cell lines (including Calu-3, A549 and H1299) revealed key lung epithelial transcripts are missing in cancer cell lines previously used to study SARS-CoV-2 infection (e.g. NKX2-1)

2. iAT2 cells cultured in an air-liquid interface (ALI) culture maintained AT2 like identity (shown by scRNA seq)

3. iAT2s and iAT2s cultured in ALI express ACE2 and TMPRSS2 however in a reduced manner compared to primary AT2s

Summary 

The authors describe the development of human induced pluripotent stem cells (iPSCs) derived alveolar epithelial type 2 (iAT2) cells. These iAT2 cells were cultured in an air-liquid interface (ALI) culture and were shown to resemble primary AT2 cells on a transcriptional level. iAT2 cells cultured in ALI were compared to previously described iPSC-derived airway basal cells (iBCs) cultured in ALI and both expressed ACE2 and TMPRSS2, important factors for SARS-CoV-2 infection. The iAT2 and iBC organoid cultures therefore provide a useful tool in studying the infection biology of SARS-Cov-2 of the lung epithelium. 

Impact for SARS-CoV2/COVID19 research efforts

Understand the virology and/or cell biology of SARS-CoV2/COVID19

Develop a vaccine for SARS-CoV2/COVID19

Study Type

· In silico study / bioinformatics study

· In vitro study

Strengths and limitations of the paper

Novelty: The authors report an iPS- derived alveolar type 2 epithelial cells that could be cultured in a 2D air liquid interface.

Standing in the field: While the cell culture model and technique is novel, it does not provide new information about COVID-19 pathogenesis. Instead it provides contributing data towards existing literature, of using cell culture models as an essential tool to study COVID-19 pathogenesis

Appropriate statistics: How statistical analysis was performed is not stated in the methods

Viral model used: no virus was used

Translatability: iAST2 ALI culture could be used to model SARS-CoV-2 infection, however the differentiation of human iPSCs to iAST2 cells is time and labour intensive

Main limitations:

· Figure 1: colour coding of ethnicity, sex and source makes it hard to distinguish different samples

· Figure 3F: on which day of the culture were the iAT2 analysed?

· Figure 6B: more biological replicates would be needed to draw conclusions as only one primary human colon sample was used as ctrl, however authors state that these are preliminary results