Reprogramming hierarchy in mouse liver cell subpopulations depends on cell intrinsic factors including BAF complex members.

Recently, various studies have tried to address this impounding question by reprogramming various cell populations. It had been successfully shown that stem/progenitor cells derived from different organs reprogram more efficiently than their differentiated counterparts thus unveiling a hierarchical reprogramming efficiency in the cells from different organs. Nevertheless, the molecular mechanisms governing this graded reprogramming phenomenon were yet to be explored. To analyse the molecular players behind this grading in reprogramming, we aimed to investigate the reprogramming capacity of different types of cells from liver parenchyma, an endodermal derived organ. In our study we found that different types of liver cells exhibit a kind of hierarchy during reprogramming towards induced pluripotent stem cells. More precisely, liver progenitor cells (LPCs) showed 275-fold superiority in reprogramming compared to differentiated liver cells (non-LPCs). When subjected to various molecular tests, LPCs endogenously express certain reprogramming factors but omission of those factors still did not allow successful reprogramming. On the other hand, LPCs showed higher reprogramming efficiencies with similar proliferation rates as their differentiated equivalents thus ruling out the effect of proliferation but impressing on the association of expression of endogenous pluripotency factors on higher reprogramming efficiencies. The presence of BAF (Brg1/Brm associated factor)-complex members Baf155 and Brg1 appeared to mediate the superior reprogramming in LPCs compared to non-LPCs as the knockdown of these BAF complex members annulled the increase reprogramming efficiencies of LPCs compared to non-LPCs