Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells

Aditya Mithal, Amalia Capilla, Dar Heinze, Andrew Berical, Carlos Villacorta-Martin, Marall Vedaie, Anjali Jacob, Kristine Abo, Aleksander Szymaniak, Megan Peasley, Alexander Stuffer, John Mahoney, Darrell N. Kotton, Finn Hawkins and Gustavo Mostoslavsky ()
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Aditya Mithal: Center for Regenerative Medicine of Boston University and Boston Medical Center
Amalia Capilla: Center for Regenerative Medicine of Boston University and Boston Medical Center
Dar Heinze: Center for Regenerative Medicine of Boston University and Boston Medical Center
Andrew Berical: Center for Regenerative Medicine of Boston University and Boston Medical Center
Carlos Villacorta-Martin: Center for Regenerative Medicine of Boston University and Boston Medical Center
Marall Vedaie: Center for Regenerative Medicine of Boston University and Boston Medical Center
Anjali Jacob: Center for Regenerative Medicine of Boston University and Boston Medical Center
Kristine Abo: Center for Regenerative Medicine of Boston University and Boston Medical Center
Aleksander Szymaniak: Cystic Fibrosis Foundation Therapeutics Lab
Megan Peasley: Cystic Fibrosis Foundation Therapeutics Lab
Alexander Stuffer: Cystic Fibrosis Foundation Therapeutics Lab
John Mahoney: Cystic Fibrosis Foundation Therapeutics Lab
Darrell N. Kotton: Center for Regenerative Medicine of Boston University and Boston Medical Center
Finn Hawkins: Center for Regenerative Medicine of Boston University and Boston Medical Center
Gustavo Mostoslavsky: Center for Regenerative Medicine of Boston University and Boston Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Efficient generation of human induced pluripotent stem cell (hiPSC)-derived human intestinal organoids (HIOs) would facilitate the development of in vitro models for a variety of diseases that affect the gastrointestinal tract, such as inflammatory bowel disease or Cystic Fibrosis. Here, we report a directed differentiation protocol for the generation of mesenchyme-free HIOs that can be primed towards more colonic or proximal intestinal lineages in serum-free defined conditions. Using a CDX2eGFP iPSC knock-in reporter line to track the emergence of hindgut progenitors, we follow the kinetics of CDX2 expression throughout directed differentiation, enabling the purification of intestinal progenitors and robust generation of mesenchyme-free organoids expressing characteristic markers of small intestinal or colonic epithelium. We employ HIOs generated in this way to measure CFTR function using cystic fibrosis patient-derived iPSC lines before and after correction of the CFTR mutation, demonstrating their future potential for disease modeling and therapeutic screening applications.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13916-6

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DOI: 10.1038/s41467-019-13916-6

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