Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing
Nature Medicine 23, 878 (2017).
doi:10.1038/nm.4355
Authors: Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans & Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing. Two potential compounds, XAV939 and rapamycin, decreased proliferation in FAP-COs, but also affected cell proliferation in wild-type COs, which thus limits their therapeutic application. By contrast, we found that geneticin, a ribosome-binding antibiotic with translational 'read-through' activity, efficiently targeted abnormal WN...
Source: Nature Medicine - Category: General Medicine Authors: Miguel Crespo Eduardo Vilar Su-Yi Tsai Kyle Chang Sadaf Amin Tara Srinivasan Tuo Zhang Nina H Pipalia Huanhuan Joyce Chen Mavee Witherspoon Miriam Gordillo Jenny Zhaoying Xiang Frederick R Maxfield Steven Lipkin Todd Evans Shuibing Chen Tags: Letter Source Type: research
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