Heterogeneous groups of alveolar type II cells in lung homeostasis and repair

Abstract

Alveoli are the gas-exchanging units of the lung, and the alveolar barrier is often a key battleground where pathogens, allergens, and other insults from the environment are encountered. This is seen in the current coronavirus disease 2019 (COVID-19) pandemic, as alveolar epithelium is one of the major targets of SARS-COV-2, the virus that causes COVID-19. Thus, it is essential to understand the mechanisms in order to maintain the integrity of alveoli epithelium. Alveolar type II (AT2) cells behave as tissue stem cells that repair alveoli epithelium during steady-state replacement and after injury. However, not all AT2 cells are equal in their ability for self-renewal or differentiation. Through marker gene identification, lineage tracing, and single-cell RNA-sequencing (scRNA-seq), distinct subpopulations of AT2 cells have been identified that play the progenitor role in a different context. The revelation of AT2 heterogeneity has brought new insights into the role of AT2 cells in various lung disease settings and potentiates the finding of more therapeutics targets. In this mini review, we discuss the recently identified subpopulations of AT2 cells and their functions under steady-state, postinjury, and pathological conditions.

Keywords: alveoli; lung; progenitor; stem cells; type II cells.

Fig. 1.

A model. During steady-state homeostasis, only a subgroup of alveolar type II cells (AT2) behave as progenitor cells and are engaged in the replacement of lost alveolar type I cells (AT1) or AT2. After injury, a larger number of AT2 are activated and behave like progenitor cells. Some of the activated AT2 differentiate into specific subpopulations that are in the middle of AT2 to AT1 transition process. Many of these intermediate subpopulations eventually differentiate into AT1 and repair the injured alveolar epithelium.