The liver possesses a remarkable capacity to regenerate, but what is the source of new cells during regeneration? The two epithelial cell populations – hepatocytes and cholangiocytes – can proliferate upon injury, but there is also evidence for the existence of an adult stem/progenitor cell, the liver progenitor cell (LPC), which resides in or near bile ducts and has both hepatocytic and cholangiocytic potential. Here (p. ), Naoki Tanimizu and co-workers investigate the abundance and potential of LPCs from neonatal and adult mice. They find that the number of LPCs decreases during postnatal life, and also observe a change in their differentiation potential: adult LPCs are strongly biased towards the cholangiocyte fate and have very limited ability for hepatocytic differentiation, both in vitro and in vivo. Mechanistically, the authors show that the transcription factor grainyhead-like 2 (GRHL2), which is known to promote cholangiocyte differentiation, is more strongly expressed in adult LPCs than neonatal LPCs. GRHL2 in turn inhibits expression of miRNA122, which is important for the hepatocyte lineage. Thus, upregulation of GRHL2 in adult LPCs provides an explanation for their reduced hepatocytic potential, and its inhibition may help to produce functional hepatocytes in the adult liver.
