BCi-NS1.1 cells were derived from a single basal cell from the large airway epithelium (LAE) of a healthy nonsmoker, and hSABCi-NS1.1 cells were derived from a single basal cell from the small airway epithelium (SAE) of a healthy nonsmoker.  Expression levels were determined using HiSeq 4000 RNA-seq data at day 0 (baseline) and after 28 days on an air-liquid interface (ALI).  Notable findings include:

- Both cell lines showed an increase in ACE2 expression after 28 days of differentiation
- ADAM10, ADAM17, FURIN, CTSL, and PI4KB expression was relatively maintained throughout differentiation in both cell lines
- TMPRSS2 was notably less expressed in undifferentiated LAE basal cells than in SAE basal cells, and their expression increased.  However, its expression was maintained in SAE basal cells.  
- TPRSS11A and TMPRSS11D expression remained low in both LAE and SAE cells throughout differentiation

Because these cell lines are immortal, they may continue to be useful in SARS-CoV-2 research - especially for early drug screening.  

ACE2 and Other Cellular Proteins Related to B-Coronavirus Infection Expression Increases in Basal Cells from the Large Airway Epithelium Throughout Differentiation

Zhang et al. developed two immortal cell lines from the airway epithelial basal cells of healthy nonsmokers.  The BCi-NS1.1 cell line originated from the large airway epithelium (LAE), and the hSABCi-NS1.1 cell line originated from the small airway epithelium (SAE).  These cells were found to express genes relevant to a SARS-CoV-2 infection, including ACE2 and TMPRSS2.  Furthermore, they are genetically pliable.  Zhang et al. believe that they may be useful for studying the pathogenesis of COVID-19 as well as potential therapeutics.  

Michigan State University

- developed by Partridge et al.
- developed by Zhang et al. 

Cell Lines Used to Study COVID-19

Zhang, H., Rostami, M. R., Leopold, P. L., Mezey, J. G., O'Beirne, S. L., Strulovici-Barel, Y., & Crystal, R. G. (2020). Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. American Journal of Respiratory and Critical Care Medicine, (ja).
https://www.atsjournals.org/doi/full/10.1164/rccm.202003-0541OC
doi: 10.1164/rccm.202003-0541OC   

Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium

Partridge et al. determined which human cell line model to use for studying SARS-CoV-2 S protein attachment based off of the mRNA expression of different membrane proteins important to the pathogenesis of COVID-19.  They investigated the following cell types:

- RT4 urinary bladder epithelial cell line
- A549  lung adenocarcinoma alveolar basal epithelial cell line
- Caco2 colorectal adenocarcinoma cell line
- HaCaT skin keratinocyte cell line

RT4 was determined to be the best cell line to use because it expresses both ACE2 and TMPRSS2 which directly interact with SARS-CoV-2 S protein.  It also expresses the following accessory proteins relevant to S protein attachment:

- ADAM17: a metalloprotease that processes ACE2
- rhomboid-like 2 (RHBDL2): a protease that is involved with the function of ADAM17
- CD9: an adaptor protein that controls ADAM17

Learn Before

Related

Learn After