The purpose of this research proposal is to study the morphology, function and cellular physiology of the progenitor cell niche in the normal and diseased liver. Local adult progenitor cell niches are special microenvironments that contain somatic progenitor cells (ASPCs). The latter are generally slow-cycling cells which give rise to transit amplifying cells (TACs) that leave the niche. TACs cycle faster than progenitor cells but have a limited proliferation potential. The niche also contains non-stem niche cells, axonal processes of neurons and specialized extracellular matrix. A complex molecular crosstalk between the progenitor cells and the non-stem niche cells ensures that progenitor cells divide asymmetrically, producing one daughter progenitor cell and one daughter cell that becomes a TAC.