Several studies point to possible functional roles for stochastic
heterogeneity in epithelia. For instance, the patchy arrangement of
cilia in the mouse airway epithelium generates a locally heterogeneous
flow of airway clearance that is globally efficient39.
Heterogeneity and stochastic growth have also been proposed to regulate
biliary epithelial tissue remodelling, which is central to liver
regeneration11. Further, T cells can infiltrate
through the endothelial Basement membrane containing Laminin 4 but not
through endothelial BM containing Laminin 540 during
Experimental
Autoimmune Encephalomyelitis (EAE) (Fig.1c). Heterogeneity is also
associated with pathological conditions such as
ageing41,42. For instance, cell-cell variations in
levels of protein expression is higher in old mice as compared to young
mice43. Additionally, stochastic physical
heterogeneity is shown to regulate essential physiological functions of
the tissues. For instance, mechanical heterogeneity regulates collective
cell migration during epithelial wound closure44,45.
Another evidence was reported in developing zebrafish where fluctuations
in cellular stresses regulates anteroposterior body axis formation46,47. Studies also implicate physical heterogeneity
in pathological situations such as Asthma48, pulmonary
fibrosis49 and cancer
metastasis50,51.
Overall, these studies indicate functional relevance of heterogeneity in
biological tissues. The relevance of inherent heterogeneity on disease
initiation remains largely unexplored. In the next section, we summarize
reports suggesting that inherent tissue heterogeneity might regulate
both the initiation and progression of diseases, emphasizing on cancer
initiation.