The Organoid and Cell Culture Core

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SUMMARY The Organoid and Cell Culture Core (OCCC) will contribute to the mission of the Columbia University Digestive and Liver Disease Research Center (CU-DLDRC) by serving members’ needs related to human and murine cell culture systems for modeling of gastrointestinal, hepatobiliary and pancreatic diseases. These systems include primary culture, genetically-engineered cell lines, spheroids and organoids as well as 3D co-culture. OCCC platforms will benefit the majority of clinical and basic CU-DLDRC investigators, providing powerful tools to study epithelial cells and their interactions in digestive homeostasis and disease, the central theme of the CU-DLDRC. Directed by Drs. Hiroshi Nakagawa, MD, PhD and Kelley Yan, MD, PhD, two scientists with long-standing complementary expertise in advanced cell culture and organoids, the OCCC will provide services, technologies, quality control and cost-effectiveness to the CU-DLDRC investigators, including the Pilot and Feasibility grant recipients. The OCCC will provide a rich repository of cell lines and human and mouse organoids that are well annotated for identity, passage number, and Mycoplasma infection-free status, thereby providing quality control, rigor and reproducibility. The OCCC will also assist CU-DLDRC investigators to generate 3D organoids from their human and mouse tissues as well as from inducible pluripotent stem (iPS) cells, to analyze growth, morphology, gene expression, and cell-cell interactions via co-culture experiments. The OCCC will integrate advanced cell culture technologies for manipulating genome and gene expression via CRISPR/Cas9, RNA interference, and inducible retroviral/lentiviral gene expression vectors in cell and organoid-based systems. These approaches are further enhanced by coordinated multi-core workflows with the Clinical Biospecimen and Research Core for patient- and disease-specific organoids; with the Bioinformatics and Single Cell Analysis Core for the plate-RNAseq-based CRISPR and drug screens; and with the Bioimaging Core for functional visualization of cells and organoids. The OCCC will promote the mission of the CU-DLDRC through the following interrelated Specific Aims: To provide CU-DLDRC members and their laboratories with cell lines, advanced cell culture platforms and technologies (Aim 1); to build and expand unique CU-DLDRC and national repositories of disease- specific human and mouse 3D organoid libraries (Aim 2); and to enhance the technical capabilities of new and established CU-DLDRC investigators through training on cell and organoid culture models and as well as educational seminars on novel developments (Aim 3). The OCCC will be highly utilized with 71% of CU-DLDRC members indicating use, most of them use of multiple OCCC services. In summary, the OCCC will provide highly efficient and cost-effective services and unique models that do not currently exist in CU-DLDRC members’ laboratory and therefore constitute significant benefits. Through its services, OCCC will stimulate translational science and collaborations in the CU-DLDRC and contribute to its mission to promote digestive disease science.