Table 1.
Summary of the specific markers that enable the precise identification of the epithelial stem/progenitor cell subpopulations present within the lung.
| Cell Type | Location | Markers | Differentiation Potential | Refs. |
|---|---|---|---|---|
| Basal cells (BCs) | Epithelium in the trachea and bronchioles | TP63, KRT5, KRT14, NGFR, PDPN, KRT8, N2ICD, and c-Myb/TP73 |
Self-renewal; AT1, AT2 basal luminal precursor cell, neuroendocrine cells, ionocytes CCs, GCs, and ciliated cells |
[23,87,88,89,90,91,92,93,94] |
| Variant club cells/ Clara cells |
Bronchi and bronchioles (epithelium) | SCGB1A1 and CYP2F2− | Self-renewal: GCs and ciliated cells | [82,95,96] |
| Neuroendocrine cells (PNECs) | Epithelium, at branching points in the bronchi and bronchioles | GRP, ASCL1, CXCR4, NCAD and ROBO | Multiciliated cells and secretory cells | [49,55,97,98,99,100] |
| Broncho-alveolar stem cells (BASCs) | Epithelium and distal airway alveolar sacs | SCGB1A1 and SFTPC | Self-renewal: AT2 Ciliated cells: GCs and AT1 |
[101,102,103,104] |
| AT2 | Distal airway alveolar sacs | SFTPC and LysM | Self-Renewal: AT1, SCA1+ mesenchymal progenitors, SFTPC+ AT1 progenitors, |
[66,83,105,106,107,108] |
| Distal airway stem cells (DASCs), Alveolar progenitor |
Distal airways, bronchioles, and alveolar regions | TP63 and KRT5 | Self-Renewal: AT2 | [84] |
| Self-Renewal: | [86] | |||
| AT2, SCGB1A1+, and CYP2F2+ CCs | [86,96] | |||
| AT1 | HOPX, | AT2 | [84] | |
| Club cells, ciliated cells | Terminal bronchioles and less in the respiratory bronchioles, trachea, and bronchioles |
SCGB1A1, and CYP2F2 | BCs | [86] |
| Ciliated cells | [96] | |||
| TubIVa and FOXJ1 | GCs | [109] | ||
| Integrin α6β4+ alveolar progenitor | Terminal bronchioles, broncho-alveolar junctions, and less in the respiratory bronchioles | SCGB1A1−, SPC−, ITGα6, and ITGβ4 | Self-Renewal: AT1 Ciliated cells: AT2 and CCs |
[96] |
Abbreviations: ASCL-1, achaete-scute homolog 1; AT1/2, alveolar type 1/2 cells; BCs, basal cells; CCs, club cells; c-Myb, transcription factor; CYP2F2, cytochrome P450 family 2 subfamily f member 2; CXCR4, chemokine receptor; FOXJ1, transcription factor of fox family; GCs, goblet cells; GRP, bombesin or gene-related peptide; HOPX, homeodomain-only protein; ITG, integrin; KRT, cytokeratin; LysM, lysozyme M; N2ICD, Notch intracellular domain 2; NCAD, N-cadherin; NGFR, nerve growth factor receptor; PDPN, podoplanin; ROBO, roundabout receptor; SCA-1, stem cell antigen-1; SCGB1A1, secretoglobin 1A1; SFTPC, surfactant protein C; TP, tumor protein; and TubIVa, human tubulin beta class Iva.