Autonomous induction of hepatic polarity to construct single cell liver

Symmetry breaking of protein distribution and cytoskeleton organization is an essential aspect for development of apico-basal polarity. In embryonic cells this process is largely cell autonomous, while differentiated epithelial cells collectively polarize during epithelium formation. We report here that the polarization of mature hepatocytes is a cell autonomous process. Single hepatocytes developed secretory hemi-apical lumens upon adhesion to finely tuned substrates bio-functionalized with cadherin and extra cellular matrix. The creation of this single cell liver allows unprecedented control and imaging resolution of the lumenogenesis process. We demonstrate that the density and localization of cadherins along the initial cell-cell contact acted as a key factor triggering the reorganization from lateral to apical actin cortex. Consequently, we established why hepatocytes could form asymmetric lumens in heterotypic doublets involving another ectopic epithelial cell originating from kidney, breast, or colon.