Research Information
The Stem Cell Differentiation Core provides patient-specific, stem cell-based models that enable investigators to test CFTR function and its rescue through various approaches including, but not limited to, modulator therapy, read-through agents, and genetic based therapies. Starting from CF patient-iPSCs or genetically modified iPSCs, the core generates airway epithelium through state-of-the-art directed differentiation protocols and will provide the derived epithelium in organoid cultures [1] or air-liquid interface (ALI) cultures [2,3] to core users for further study.
The Stem Cell Differentiation Core was established in 2024 in response to the need demonstrated by the CF community for support in the access and utilization of patient-specific, stem cell-based in vitro models. Specifically, the Core is designed to fulfill two key functions:
Core function #1: Provide iPSC-derived airway epithelium
· iPSC-derived airway organoid culture format. This culture format is suitable for subsequent CFTR functional assessments, such as forskolin-induced swelling (FIS).
· iPSC-derived ALI culture format. This culture format is suitable for subsequent functional assays such as Ussing chamber analysis and micro-Optical Coherence Tomography (µOCT) imaging.
Core function #2: Perform characterization and quality control of iPSC-derived airway epithelium.
The core confirms the quality of generated airway epithelia with thorough analyses during differentiation and on obtained cultures. This quality control ensures that we are providing consistent “quality” of cultures so users can reliably use without issues arising. This documentation for each released lot will be provided to Core users to support subsequent publication and/or grant writing.
In addition, the core houses multiple CF iPSC lines as well as genetically modified iPSC lines to share and differentiate. In conjunction with the RDP Gene Expression and Editing Core, we support investigators generating modified iPSCs as desired. Similarly, together with RDP Functional Assay Core, we guide investigators to appropriate and available functional assays in the CFRC. We welcome any investigators and trainees to consult study designing or to learn the technologies to implement to their laboratories.
Contact Information
Core users are associated both within and beyond the CF Research Center; there is no limitation on who may access the Core. For additional information regarding resources and services, please contact:
Selected References
1. Li C, Liu Z, Anderson J, Liu Z, Tang L, Li Y, Peng N, Chen J, Liu X, Fu L, Townes TM, Rowe SM, Bedwell DM, Guimbellot J, Zhao R. Prime editing-mediated correction of the CFTR W1282X mutation in iPSCs and derived airway epithelial cells. PLoS One. 2023;18(11):e0295009. Epub 20231129. doi: 10.1371/journal.pone.0295009. PubMed PMID: 38019847; PMCID: PMC10686454.
2. Hawkins FJ, Suzuki S, Beermann ML, Barilla C, Wang R, Villacorta-Martin C, Berical A, Jean JC, Le Suer J, Matte T, Simone-Roach C, Tang Y, Schlaeger TM, Crane AM, Matthias N, Huang SXL, Randell SH, Wu J, Spence JR, Carraro G, Stripp BR, Rab A, Sorsher EJ, Horani A, Brody SL, Davis BR, Kotton DN. Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells. Cell Stem Cell. 2021;28(1):79-95 e8. Epub 20201023. doi: 10.1016/j.stem.2020.09.017. PubMed PMID: 33098807; PMCID: PMC7796997.
3. Suzuki S, Hawkins FJ, Barilla C, Beermann ML, Kotton DN, Davis BR. Differentiation of human pluripotent stem cells into functional airway basal stem cells. STAR Protoc. 2021;2(3):100683. Epub 20210720. doi: 10.1016/j.xpro.2021.100683. PubMed PMID: 34355203; PMCID: PMC8322461