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  1. AU="Peasley, Megan"
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  1. Artikel ; Online: Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells.

    Mithal, Aditya / Capilla, Amalia / Heinze, Dar / Berical, Andrew / Villacorta-Martin, Carlos / Vedaie, Marall / Jacob, Anjali / Abo, Kristine / Szymaniak, Aleksander / Peasley, Megan / Stuffer, Alexander / Mahoney, John / Kotton, Darrell N / Hawkins, Finn / Mostoslavsky, Gustavo

    Nature communications

    2020  Band 11, Heft 1, Seite(n) 215

    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 ...

    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 CDX2
    Mesh-Begriff(e) CDX2 Transcription Factor/metabolism ; Cell Differentiation ; Cystic Fibrosis ; Epithelial Cells ; Gene Knock-In Techniques ; Genetic Vectors ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Intestine, Small ; Intestines/physiology ; Mesoderm/metabolism ; Organoids/cytology ; Organoids/metabolism ; Thyroid Nuclear Factor 1/genetics
    Chemische Substanzen CDX2 Transcription Factor ; CDX2 protein, human ; NKX2-1 protein, human ; Thyroid Nuclear Factor 1
    Sprache Englisch
    Erscheinungsdatum 2020-01-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-13916-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: A multimodal iPSC platform for cystic fibrosis drug testing.

    Berical, Andrew / Lee, Rhianna E / Lu, Junjie / Beermann, Mary Lou / Le Suer, Jake A / Mithal, Aditya / Thomas, Dylan / Ranallo, Nicole / Peasley, Megan / Stuffer, Alex / Bukis, Katherine / Seymour, Rebecca / Harrington, Jan / Coote, Kevin / Valley, Hillary / Hurley, Killian / McNally, Paul / Mostoslavsky, Gustavo / Mahoney, John /
    Randell, Scott H / Hawkins, Finn J

    Nature communications

    2022  Band 13, Heft 1, Seite(n) 4270

    Abstract: Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established ... ...

    Abstract Cystic fibrosis is a monogenic lung disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator anion channel, resulting in significant morbidity and mortality. The progress in elucidating the role of CFTR using established animal and cell-based models led to the recent discovery of effective modulators for most individuals with CF. However, a subset of individuals with CF do not respond to these modulators and there is an urgent need to develop novel therapeutic strategies. In this study, we generate a panel of airway epithelial cells using induced pluripotent stem cells from individuals with common or rare CFTR variants representative of three distinct classes of CFTR dysfunction. To measure CFTR function we adapt two established in vitro assays for use in induced pluripotent stem cell-derived airway cells. In both a 3-D spheroid assay using forskolin-induced swelling as well as planar cultures composed of polarized mucociliary airway epithelial cells, we detect genotype-specific differences in CFTR baseline function and response to CFTR modulators. These results demonstrate the potential of the human induced pluripotent stem cell platform as a research tool to study CF and in particular accelerate therapeutic development for CF caused by rare variants.
    Mesh-Begriff(e) Animals ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Epithelial Cells/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Ion Transport
    Chemische Substanzen Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
    Sprache Englisch
    Erscheinungsdatum 2022-07-29
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-31854-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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