Photochemically Activated Notch Signaling Hydrogel Preferentially Differentiates Human Derived Hepatoblasts to Cholangiocytes

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2021
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Rizwan, Muhammad
Fokina, Ana
Kivijärvi, Tove
Ogawa, Mina
Laselva, Onofrio
Smith, Laura J.
Bear, Christine E.
Ogawa, Shinichiro
Shoichet, Molly S.
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Advanced Functional Materials. Wiley. 2021, 31(5), 2006116. ISSN 1616-301X. eISSN 1616-3028. Available under: doi: 10.1002/adfm.202006116
Zusammenfassung

Cholangiocytes form an intricate network of bile ducts to enable proper liver function; yet, recapitulating human stem cell differentiation to cholangiocytes in vitro requires Notch signaling and soluble ligands do not activate the Notch pathway. To overcome these limitations, jagged1 is immobilized on a chemically defined hyaluronan to specifically differentiate human embryonic stem cell‐derived hepatoblasts to cholangiocytes. Hepatoblasts cultured on the jagged1‐hydrogels upregulate Notch target genes and express key cholangiocyte markers including cystic fibrosis transmembrane conductance regulator. Moreover, cholangiocytes adopt morphological changes that resemble liver biliary structures. To emulate natural biliary system development, a new strategy is developed to achieve spatiotemporal control over the Jagged1–Notch2 interaction: jagged1 is first caged with a photocleavable streptavidin and then it is uncaged photochemically to restore the biological function of Jagged1, which is confirmed with Notch2 activation in a fluorescent reporter cell line. Moreover, the differentiation of human embryonic stem cell‐derived hepatoblasts to cholangiocytes is temporally controlled with photochemical uncaging of this streptavidin‐Jagged1‐immobilized hyaluronan hydrogel. This strategy defines a framework to control protein signaling in time and space and specifically for Notch signaling for ultimate use in regenerative medicine strategies of the liver.

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ISO 690RIZWAN, Muhammad, Ana FOKINA, Tove KIVIJÄRVI, Mina OGAWA, Markus KUFLEITNER, Onofrio LASELVA, Laura J. SMITH, Christine E. BEAR, Shinichiro OGAWA, Molly S. SHOICHET, 2021. Photochemically Activated Notch Signaling Hydrogel Preferentially Differentiates Human Derived Hepatoblasts to Cholangiocytes. In: Advanced Functional Materials. Wiley. 2021, 31(5), 2006116. ISSN 1616-301X. eISSN 1616-3028. Available under: doi: 10.1002/adfm.202006116
BibTex
@article{Rizwan2021Photo-51874,
  year={2021},
  doi={10.1002/adfm.202006116},
  title={Photochemically Activated Notch Signaling Hydrogel Preferentially Differentiates Human Derived Hepatoblasts to Cholangiocytes},
  number={5},
  volume={31},
  issn={1616-301X},
  journal={Advanced Functional Materials},
  author={Rizwan, Muhammad and Fokina, Ana and Kivijärvi, Tove and Ogawa, Mina and Kufleitner, Markus and Laselva, Onofrio and Smith, Laura J. and Bear, Christine E. and Ogawa, Shinichiro and Shoichet, Molly S.},
  note={Article Number: 2006116}
}
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