Basal to sulfur dioxide injury (Rock et al.,

Basal cells, located in tracheobronchial region, are considered as one of the major tissue-specific stem cells in the upper airways marked by the expression of transcription factors Trp63, surface receptor NGFR, GSI?4 lectin and cytokeratin5 (Krt5). They are able to self-renew and give rise secretory and ciliated cells (Tata et al., 2013). In addition to maintaining local epithelial homeostasis, basal stem cells can respond to sulfur dioxide injury (Rock et al., 2009) or naphthalene injury (Hong, 2003), and migrate to repopulate alveolar epithelium after H1N1 influenza infection (Kumar et al., 2011). The differentiation of basal cells is regulated by Notch signaling which is altered in certain injury conditions.

            Recent lineage tracing studies further dissect the distinct subpopulations of basal cells and their functional differences in homeostatic and injury conditions. During homeostasis, rare expression of Krt14 is found in either basal stem cells (BSCs) or basal luminal precursor cells (BLPCs) both expressing Trp63 and Krt5. After injury, the expression of Krt14 is remarkably up-regulated and the proportion of Krt5+Krt14+ cells increases (Cole et al., 2010; Ghosh et al., 2011), suggesting Krt14 could serve as a maker for activated basal stem cells. BLPCs are the progeny of BSCs with a lower rate of self-renewal and differentiation, and can be distinguished from BSCs by its Krt8 expression (Watson et al., 2015). A study using Notch transgeneic mice showed Notch3 signaling regulates the expansion and differentiation of basal population that deletion of Notch3 results in an increased number of both BSCs and Krt5+Krt8 basal cells, but not in other epithelial lineages (Mori et al., 2015). Additionally, a new study showed Trp63+ basal cells specific segregate into two distinct subpopulations-N2ICD+ (the active Notch2 intracellular domain) and c-Myb+ cells after injury, but not in homeostatic conditions. These two basal populations exhibit distinct differentiation potentials that N2ICD+ cells generate mature secretory lineage cells whereas c-Myb+ cells only give rise to ciliated cells (Pardo-Saganta et al., 2015).

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