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000307578 1001_ $$aBregante, Javier$$b0
000307578 245__ $$aHuman liver cholangiocyte organoids capture the heterogeneity of in vivo liver ductal epithelium.
000307578 260__ $$aMaryland Heights, MO$$bCell Press$$c2026
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000307578 520__ $$aHuman liver ductal epithelium is morphologically, functionally, and transcriptionally heterogeneous. Understanding the impact of this heterogeneity has been challenging due to the absence of systems that recapitulate this heterogeneity in vitro. Here, we found that human liver cholangiocyte organoids do not retain the complex cellular heterogeneity of the native ductal epithelium. Inspired by the knowledge of the cellular niche, we refined our previous organoid medium to fully capture the in vivo cellular heterogeneity. We employed this refined system to analyze the relationships between human biliary epithelial cell states. In our refined model, cholangiocytes transition toward hepatocyte-like states through a bipotent state. Additionally, inhibiting WNT signaling enhances the differentiation capacity of the cells toward hepatocyte-like states. By capturing the in vivo cholangiocyte heterogeneity, our improved organoid model represents a platform to investigate the impact of the different liver ductal cell states in cell plasticity, regeneration, and disease.
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000307578 650_7 $$2Other$$aCP: developmental biology
000307578 650_7 $$2Other$$aCP: stem cell research
000307578 650_7 $$2Other$$abipotent
000307578 650_7 $$2Other$$acell state
000307578 650_7 $$2Other$$acholangiocyte
000307578 650_7 $$2Other$$aductal cell
000307578 650_7 $$2Other$$ahepatocyte-like
000307578 650_7 $$2Other$$aheterogeneity
000307578 650_7 $$2Other$$ahuman liver
000307578 650_7 $$2Other$$aorganoids
000307578 650_7 $$2Other$$arefined medium
000307578 650_7 $$2Other$$ascRNA-seq
000307578 7001_ $$aDon, Flaminia Kaluthantrige$$b1
000307578 7001_ $$aRost, Fabian$$b2
000307578 7001_ $$aGohr, André$$b3
000307578 7001_ $$aBelenguer, Germán$$b4
000307578 7001_ $$0P:(DE-He78)72df4d93958e20035caea8fbcd4b166a$$aBaenke, Franziska$$b5$$udkfz
000307578 7001_ $$aLiabeuf, Dylan$$b6
000307578 7001_ $$aPöche, Jessie$$b7
000307578 7001_ $$aSchafmayer, Clemens$$b8
000307578 7001_ $$aWilsch-Bräuninger, Michaela$$b9
000307578 7001_ $$aHinz, Sebastian$$b10
000307578 7001_ $$aHolleran, Kevin O'$$b11
000307578 7001_ $$0P:(DE-HGF)0$$aStange, Daniel E$$b12
000307578 7001_ $$aHuch, Meritxell$$b13
000307578 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2025.116786$$gVol. 45, no. 1, p. 116786 -$$n1$$p116786$$tCell reports$$v45$$x2211-1247$$y2026
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