PMID- 35777357 OWN - NLM STAT- MEDLINE DCOM- 20220715 LR - 20220812 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 17 IP - 7 DP - 2022 Jul 12 TI - Small-molecule inhibitor cocktail promotes the proliferation of pre-existing liver progenitor cells. PG - 1589-1603 LID - S2213-6711(22)00276-4 [pii] LID - 10.1016/j.stemcr.2022.05.023 [doi] AB - A recent study showed that a cocktail of three small molecules, Y-27632, A83-01, and CHIR99021 (YAC), converts mature hepatocytes (MHs) into proliferative bipotent cells that can be induced into MHs and cholangiocytes in rats. However, when we reproduced these experiments, it was found that bipotent cells may be derived from resident liver progenitor cells (LPCs), whose proliferative activity was promoted by YAC. A simple and efficient sorting scheme was also developed in this study to harvest high-purity and high-yield LPCs. The inducible bipotency of purified LPCs was verified; in addition, they were found to spontaneously differentiate into hepatocytes and cholangiocytes due to changes in proliferative status even without induction. Moreover, during the differentiation process, some hepatocytes spontaneously reconverted to LPCs under certain conditions, such as the release of contact inhibition. These findings may improve our understanding of LPCs and provide a cell source for regenerative medicine. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Fu, Qingjie AU - Fu Q AD - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. FAU - Ohnishi, Shunsuke AU - Ohnishi S AD - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address: sonishi@pop.med.hokudai.ac.jp. FAU - Suda, Goki AU - Suda G AD - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. FAU - Sakamoto, Naoya AU - Sakamoto N AD - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220630 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 SB - IM MH - Animals MH - Cell Differentiation MH - Cell Proliferation MH - Hepatocytes MH - *Liver MH - Rats MH - *Stem Cells PMC - PMC9287679 OTO - NOTNLM OT - cell differentiation OT - cell proliferation OT - liver development OT - liver progenitor cells OT - regenerative medicine OT - small molecules EDAT- 2022/07/02 06:00 MHDA- 2022/07/16 06:00 PMCR- 2022/06/30 CRDT- 2022/07/01 18:42 PHST- 2021/03/03 00:00 [received] PHST- 2022/05/31 00:00 [revised] PHST- 2022/05/31 00:00 [accepted] PHST- 2022/07/02 06:00 [pubmed] PHST- 2022/07/16 06:00 [medline] PHST- 2022/07/01 18:42 [entrez] PHST- 2022/06/30 00:00 [pmc-release] AID - S2213-6711(22)00276-4 [pii] AID - 10.1016/j.stemcr.2022.05.023 [doi] PST - ppublish SO - Stem Cell Reports. 2022 Jul 12;17(7):1589-1603. doi: 10.1016/j.stemcr.2022.05.023. Epub 2022 Jun 30.