This study investigates the single-cell RNA expression profile of ACE2, the receptor for SARS-CoV-2, in normal human lungs using advanced single-cell RNA sequencing (scRNA-Seq) technology. The researchers analyzed 43,134 cells from 8 adult donors and found that ACE2 expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, this population of ACE2-expressing AT2 cells also highly expressed genes that positively regulate viral entry, replication, and transmission. The study provides a biological background for understanding the epidemic of COVID-19 and could inform future anti-ACE2 therapeutic strategies. The findings suggest that SARS-CoV-2 has evolved to target this specific population of AT2 cells for its reproduction and transmission, leading to severe alveolar damage. However, the study's limitations include a small sample size and the inability to analyze protein levels at the single-cell level.This study investigates the single-cell RNA expression profile of ACE2, the receptor for SARS-CoV-2, in normal human lungs using advanced single-cell RNA sequencing (scRNA-Seq) technology. The researchers analyzed 43,134 cells from 8 adult donors and found that ACE2 expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, this population of ACE2-expressing AT2 cells also highly expressed genes that positively regulate viral entry, replication, and transmission. The study provides a biological background for understanding the epidemic of COVID-19 and could inform future anti-ACE2 therapeutic strategies. The findings suggest that SARS-CoV-2 has evolved to target this specific population of AT2 cells for its reproduction and transmission, leading to severe alveolar damage. However, the study's limitations include a small sample size and the inability to analyze protein levels at the single-cell level.