Human branching cholangiocyte organoids recapitulate functional bile duct formation

Roos, Floris J.M.; Tienderen, Gilles van; Wu, Haoyu; Bordeu, Ignacio; Vinke, Dina; Albarinos, Laura Muñoz; Monfils, Kathryn; Niesten, Sabrah; Smits, Ron; Willemse, Jorke; Rosmark, Oskar; Westergren‐Thorsson, Gunilla; Kunz, Daniel J.; Wit, Maurice de; French, Pim J.; Vallier, Ludovic; IJzermans, Jan N.M.; Bártfai, Richárd; Marks, Hendrik; Simons, Benjamin D.; Royen, Martin E. van; Verstegen, Monique M A; Laan, Luc J. W. van der

doi:10.1016/j.stem.2022.04.011

Cited by 24 publications

(44 citation statements)

References 84 publications

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“…Branching morphogenesis by branching and annihilating random walk (BARW) (Hannezo et al, 2017) has been previously used to simulate generation of mouse mammary gland (Hannezo et al, 2017; Nerger et al, 2021), kidney (Hannezo et al, 2017), pancreas (Sznurkowska et al, 2018), zebrafish nervous system (Uçar et al, 2021) and cholangiocyte organoids (Roos et al, 2022). Whether human TDLUs branch and develop with the same principles as the mouse mammary gland has not been addressed.…”

Section: Resultsmentioning

confidence: 99%

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Peurla

Paavolainen

Tammelin

et al. 2023

Preprint

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The major lactiferous ducts of the human breast branch out and ultimately end at terminal ductal lobular units (TDLUs). These glandular structures are the source of milk upon lactation, and also the most common origin of breast cancer. Despite their functional and clinical importance, the three dimensional (3D) architecture of TDLUs has remained undetermined, largely due to their absence in rodent animal models. By utilizing recent technological advances in optical tissue clearing and microscopy, we imaged the 3D structure of healthy human breast tissue to determine whether general branching patterns or cell type specific niches exist in the TDLU. Our data demonstrate that TDLUs have a consistent shape and their branch parameters are largely comparable between different TDLUs and individuals irrespective of age or parity. Simulation of TDLU branching morphogenesis in 3D by mathematical modelling suggests that evolutionarily conserved mechanisms regulate mammary gland branching in humans and mice, despite their anatomical differences. The data also demonstrate a new level of organization within the TDLU structure identifying a main branch that dominates in bifurcation events and exhibits a more duct-like keratin expression pattern. In all, our data provide the first structural insights into 3D human breast anatomy and branching, and exemplify the power of volumetric imaging in deeper understanding of human breast biology.

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Section: Resultsmentioning

confidence: 99%

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Peurla

Paavolainen

Tammelin

et al. 2023

Preprint

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show abstract

“…These approaches are undergoing rapid developments, allowing establishment of human organoids from adult/fetal human liver or pluripotent stem cells and modeling different liver diseases. 68 , 69 , 70 , 71 Different types of liver organoid models from mice, human beings, dogs, and cats now are available for several monogenic liver diseases such as Alagille syndrome, cystic fibrosis, primary sclerosing cholangitis, Wilsons disease, HBV infection, steatosis, or liver cancer, among others. 72 , 73 , 74 , 75 , 76 , 77 , 78 The generation of organoids from adult patient liver tissues also retains the genetic background of the individual patient, thus creating patient-specific disease models and enabling in-depth investigations of pathogenesis mechanisms underlying genetic diseases and cancer.…”

Section: Liver Spheroids and Organoidsmentioning

confidence: 99%

In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations

Kaur

Kidambi

Ortega‐Ribera

et al. 2023

Cellular and Molecular Gastroenterology and Hepatology

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“… 23 , 24 These cells have been used for disease modeling and drug screening in cystic fibrosis. 23 Importantly, cholangiocytes represent one of the rare hepatic cell types that can be grown in vitro as epithelial organoids while maintaining their key characteristics 25 , 26 , 27 (see separate section on primary tissue organoids) and may be used for regenerative cytotherapy applications. 28 …”

Section: Generating the Different Hepatic Cells From Hipscsmentioning

confidence: 99%

Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations

Rezvani¹,

Vallier²,

Guillot³

2023

Cellular and Molecular Gastroenterology and Hepatology

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Human branching cholangiocyte organoids recapitulate functional bile duct formation

Cited by 24 publications

References 84 publications

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast

In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations

Modeling Nonalcoholic Fatty Liver Disease in the Dish Using Human-Specific Platforms: Strategies and Limitations

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