TY - JOUR
T1 - Macrophage-derived Wnt opposes notch signaling to specify hepatic progenitor cell fate in chronic liver disease
AU - Boulter, L.
AU - Govaere, O.
AU - Bird, T.G.
AU - Radulescu, S.
AU - Ramachandran, P.
AU - Pellicoro, A.
AU - Ridgway, R.
AU - Seo, S.S.
AU - Spee, B.
AU - van Rooijen, N.
AU - Sansom, O.J.
AU - Iredale, J.P.
AU - Lowell, S.
AU - Roskams, T.A.
AU - Forbes, S.J.
PY - 2012
Y1 - 2012
N2 - Nat Med. 2012 Mar 4;18(4):572-9. doi: 10.1038/nm.2667.
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease.
Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ, Iredale JP, Lowell S, Roskams T, Forbes SJ.
Source
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Abstract
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.
Comment in
Neighborhood watch orchestrates liver regeneration. [Nat Med. 2012]
AB - Nat Med. 2012 Mar 4;18(4):572-9. doi: 10.1038/nm.2667.
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease.
Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ, Iredale JP, Lowell S, Roskams T, Forbes SJ.
Source
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
Abstract
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.
Comment in
Neighborhood watch orchestrates liver regeneration. [Nat Med. 2012]
U2 - 10.1038/nm.2667
DO - 10.1038/nm.2667
M3 - Article
SN - 1078-8956
VL - 18
SP - 572
EP - 579
JO - Nature Medicine
JF - Nature Medicine
IS - 4
ER -
