Table 1.
Stem cell type | Location | Markers | Contribution to regeneration | Differentiation outcome | WNT signaling role | Reference |
---|---|---|---|---|---|---|
Basal cells (BCs) | Trachea, bronchi (cartilaginous airways) | TRP63, KRT5 (and variably KRT14), NGFR, PDPN (T1α) | Major | Ciliated cells, secretory cells (club and goblet cells) | Increase cell expansion and direct differentiation | (Brechbuhl et al., 2011; Giangreco et al., 2012; Rock et al., 2009) |
Club cells | Trachea, bronchi and bronchioles | SCGB1A1(also known as CCSP and CC10), UPK3A |
Major | Ciliated cells, secretory cells (club and goblet cells), basal cells, AT2 cells, AT1 |
Inhibit differentiation into goblet cells by RYK receptor | (Guha et al., 2017; Lee et al., 2017; Rawlins et al., 2009; Rock et al., 2009; Tata et al., 2013) |
Submucosal gland duct cell (myoepithelial cells [MECs]) | Trachea, bronchi and bronchioles | TRP63, KRT5, KRT14, rich in ACTA2 | Minor | Trachea pithelium | Promotes the transition to basal cell phenotype | (Lynch et al., 2018) |
Neuroendocrine cells (NECs) | Bronchioles | Calcitonin gene-related peptide | Minor | Ciliated cells, club cells | Not reported | (Song et al., 2012; Yao et al., 2018) |
Bronchoalveolar stem cells (BASCs) | Bronchoalveolar duct junction | SCGB1A1, SFTPC | Major | Ciliated cells, club cells, AT1 cells, AT2 cells | Increase cell expansion | (Kim et al., 2005; Liu et al., 2019; Salwig et al., 2019; Zhang et al., 2008) |
Lineage-negative epithelial stem/progenitor (LNEP) | Alveoli | TRP63, KRT5, H2-K1high | Minor | AT1 cells, AT2 cells | Enhance differentiation into AT2 | (Kathiriya et al., 2020; Kumar et al., 2011; Vaughan et al., 2015; Xi et al., 2017; Zuo et al., 2015) |
Distal lung progenitors (SFTPC-ve AT2 cells) | Alveoli | Integrin α6β4 | Minor | Club cells, AT2 cells | Not reported | (Chapman et al., 2011) |
Alveolar type 2 cells (AT2) | Alveoli | SFTPC, AQP3, ABCA3 | Major | AT1 cells | Increase cell expansion and proper differentiation during regeneration | (Barkauskas et al., 2013; Desai et al., 2014; Nabhan et al., 2018; Olajuyin et al., 2019; Tanjore et al., 2013; Zacharias et al., 2018) |
Alveolar type 1 cells (AT1) | Alveoli | AQP5, PDPN (T1α), HOPX | Minor | AT2 cells | Not reported | (Jain et al., 2015) |