Technical advances in the development of zonation liver in vitro systems that incorporate localized Wnt activating signals
Valle-Encinas, E.; Dawes, M.; Velasco Martinez, C.; McSweeney, K.; Muller, M.; Bird, T.; Dale, T. C.
Show abstract
A Wnt microenvironment sustained by the hepatic central vein is essential for the segregation of liver functions into zones. Current liver culture systems lack localized Wnt cues and as a consequence fail to maintain the hepatocyte functional heterogeneity that is observed in the intact organ. In this study, organoid models and 2D-culture systems were used to identify cellular sources and Wnt presentation methods that could support the future development of zonated liver in vitro systems. Using soluble ligands, we show that primary hepatocyte (PH)-derived organoids but not bile duct (BD)-derived organoids may be used to recapitulate the resting liver. We provide evidence that differentiation of PH-organoids in the presence of Wnt9b and Rspo3 induce pericentral maturation. Finally, we show that immobilization of Rspo3 onto beads in combination with soluble Wnt9b may be a valid strategy to recreate the central vein Wnt microenvironment in vitro.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations 95%
- Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis 94%
- Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells 93%
Similar papers in this journal
- Single-cell morphological tracking of liver cell states to identify small-molecule modulators of liver differentiation 95%
- Inhibition of Extracellular Vesicle-Associated MMP2 Abrogates Intercellular Transfer of Hepatic miR-122 to Tissue Macrophages and Curtails Liver Inflammation 94%
- Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light 93%
Similar papers in this journal
- The interplay of TGF-β1 and cholesterol orchestrating hepatocyte cell fate, EMT, and signals for HSC activation 94%
- Patient induced pluripotent stem cell-derived hepatostellate organoids establish a basis for liver pathologies in telomeropathies 94%
- Mimicking tumor cell heterogeneity of colorectal cancer in a patient-derived organoid-fibroblast model 93%
Similar papers in this journal
- Drug metabolism activity is a Critical Intrinsic Selector for Hepatocytes to elongate cell lifespan by using a cell-killing antibiotic 95%
- Emodin-Enhanced hUC-MSC Extracellular Vesicles Alleviate Acute Pancreatitis by Targeting Inflammation and Pyroptosis 93%
- Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human. 92%
Similar papers in this journal
- Efficient transgenesis and homology-directed gene targeting in monolayers of primary human small intestinal and colonic epithelial stem cells 94%
- Negligible-Cost and Weekend-Free Chemically Defined Human iPSC Culture 94%
- MIXL1 Activation in Endoderm Differentiation ofHuman Induced Pluripotent Stem Cells 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.