Application of porcupine inhibitors in stem cell fate determination

Porcupine (Porcn), a membrane‐bound O‐acyltransferase, is an endoplasmic reticulum‐located protein that has catalytic activity. Porcn is involved in post‐translational lipid modification of wingless‐Int (Wnt) proteins and serves as an indispensable step in the Wnt proper secretion and signaling. Small‐molecule inhibitors targeting Porcn catalytic function in vitro and in vivo are of great interest not only for treating cancer and fibrotic disorders but also in the field of regenerative medicine. Although a number of studies have been conducted, the exact role of Porcn in stem cell fate is not entirely clear. In some cases, Porcn inhibition declined differentiation rate, and in others, it induced stem cell differentiation toward specific lineages. In this review, we first elaborated the Porcn catalytic activity and its inhibitors. Then, we discussed about the recently reported results of Porcn inhibitors in stem cells self‐renewal and differentiation. Porcupine (Porcn) small molecules are novel chemical agents not only for treating cancer and fibrotic disorders but also in regenerative medicine. Porcn inhibition promotes the differentiation of pluripotent stem cells into neuroectodermal and mesodermal lineages. Porcn is a critical factor during somatic cell reprogramming into stem cells.