Table 1.
Identity and Location of Putative Stem Cell Populations Mediating Tissue Repair
| Tissue and region | Stem cell | Marker genes | Daughter cells | Key signals | References |
|---|---|---|---|---|---|
| Trachea and proximal airway | Basal cell | TRP63+, KRT5+, NGFR+, PDPN+, KRT14+ | Ciliated, club, self | NOTCH | 4, 6, 7 |
| Club cell | SCGB1A1+, CYP2F2+ | Basal, ciliated, goblet, self | NOTCH, SPDEF, HDAC1/2 | 5, 9, 10, 17 | |
| Distal airway | Variant club cell | SCGB1A1+, CYP2F2−, UPK3A+ | Ciliated, club, self | NOTCH, FGF10 | 15, 17, 18 |
| NEC | ASCL1+, CGRP+, PROX1+ | Ciliated, club, self | ? | 16 | |
| DASC | TRP63+, KRT5+, KRT6+ | AEC2, club, self, AEC1? | ? | 29 | |
| LNEP | ITGA6+, ITGB4+, SFTPC−, SCGB1A1−, KRT5− | AEC2, club, self | NOTCH | 30 | |
| BADJ | BASC | SFTPC+, SCGB1A1+ | Self, club? AEC2? | WNT | 19, 20, 21, 22 |
| Alveolus | AEC2 | SFTPC+, LYZ2+ | AEC1, self | WNT, EGFR-KRAS | 20, 26, 27 |
| AEC1 | HOPX+, AQP5+, PDPN+ | AEC2, self | TGFβ | 25 | |
| ITGA6+ITGB4+SFTPC− AEC | ITGA6+, ITGB4+, SFTPC−, SCGB1A1− | AEC1, AEC2, club, self | ? | 28 | |
| Mesenchyme | Pericyte | CSPG4+, ABCG2+, PDGFRβ+, FOXD1+, GLI1+ | Myofibroblast, self | SHH, WNT-NOTCH, TGFβ, VEGF, PI3K-AKT | 35, 36, 37, 38, 39, 40 |
| Endothelium | Endothelial cell | TIE2+ | Myofibroblast | TGFβ | 47 |
| VSMC | Primed cell | ACTA2+, MYH11+, PDGFRβ+, KLF4+ | VSMC, self | PDGF-KLF4 | 43 |
?, unknown; AEC, alveolar epithelial cell; AEC1, type 1 alveolar epithelial cell; AEC2, type 2 alveolar epithelial cell; AKT, protein kinase B; BADJ, bronchioalveolar duct junction; BASC, bronchioalveolar stem cell; DASC, distal airway stem cell; EGFR, epidermal growth factor receptor; FGF10, fibroblast growth factor 10; HDAC, histone deacetylase; KLF4, Kruppel-like factor 4; KRAS, Kirsten rat sarcoma viral oncogene homolog; LNEP, lineage-negative epithelial progenitor; NEC, neuroendocrine cell; PDGF, platelet-derived growth factor; PI3K, phosphoinositide 3-kinase; SHH, sonic hedgehog; SPDEF, SAM pointed domain containing ETS transcription factor; TGFβ, transforming growth factor beta; VEGF, vascular endothelial growth factor; VSMC, vascular smooth muscle cell; WNT, wingless-type MMTV integration site family.