Roles of airway basal stem cells in lung homeostasis and regenerative medicine

Abstract

Airway basal stem cells (BSCs) in the proximal airways are recognized as resident stem cells capable of self-renewing and differentiating to virtually every pseudostratified epithelium cell type under steady-state and after acute injury. In homeostasis, BSCs typically maintain a quiescent state. However, when exposed to acute injuries by either physical insults, chemical damage, or pathogen infection, the remaining BSCs increase their proliferation rate apace within the first 24 h and differentiate to restore lung homeostasis. Given the progenitor property of airway BSCs, it is attractive to research their biological characteristics and how they maintain homeostatic airway structure and respond to injury. In this review, we focus on the roles of BSCs in lung homeostasis and regeneration, detail the research progress in the characteristics of airway BSCs, the cellular and molecular signaling communications involved in BSCs-related airway repair and regeneration, and further discuss the in vitro models for airway BSC propagation and their applications in lung regenerative medicine therapy.

Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells

“…Indeed, our pseudotime analysis revealed that FOXJ high ciliated cells were the most terminally differentiated cell type, followed by FOXJ1 low ciliated cells, multiciliated precursors, club cells, ionocytes, and finally basal cells (which were defined as the root cells in our analysis) (42)(43)(44) (Fig. 2)(SFig.…”

“…The lung epithelium primarily consists of fully differentiated cells, but injury can cause cells to dedifferentiate into their progenitors (41)(42)(43). We were interested to see if there were differences in cell differentiation among age cohorts or treatment status.…”

Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs

“…IAV infection inflicted damage to the stratified layer of the airway epithelium, accompanied by an increased population of basal cells (Fig. 4d), potentially indicating a regenerative phase following the substantial loss of multiciliated cells [48][49][50] . Co-localization of IAV NP and cytokeratin may also indicate the dedifferentiation of infected cells as reported previously 51 .…”

“…4b). Basal cells, which are adult stem cells located at the base of the airway epithelium near the basement membrane, can increase in number and differentiate into multiciliated cells in the event of an injury 42 . Immunofluorescent staining of Cytokeratin 5, a marker for basal cells, revealed an increase in the number of basal cells after infection (Fig.…”

Epithelial–immune cell interactions in allergic diseases

“…In the skin, the stratum corneum, formed by several layers of corneocytes embedded in extracellular lipids, protects the subjacent tissue [5]. A rapid turnover of cells at the surface is a common feature among epithelia in different tissues and allows for quick adaptation to insults and fast wound healing [6–8].…”