TY - JOUR T1 - Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells JF - bioRxiv DO - 10.1101/118034 SP - 118034 AU - Michael K. Dame AU - Durga Attili AU - Shannon D. McClintock AU - Priya H. Dedhia AU - Peter Ouilette AU - Olaf Hardt AU - Alana M Chin AU - Xiang Xue AU - Julie Laliberte AU - Erica L Katz AU - Gina M Newsome AU - David Hill AU - Alyssa Miller AU - David Agorku AU - Christopher H Altheim AU - Andreas Bosio AU - Becky Simon AU - Linda C Samuelson AU - Jay A Stoerker AU - Henry D Appelman AU - James Varani AU - Max S. Wicha AU - Dean E. Brenner AU - Yatrik M. Shah AU - Jason R Spence AU - Justin A. Colacino Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/18/118034.abstract N2 - The intestine is maintained by stem cells, marked by LGR5 expression, located at the base of crypts. Genetically engineered mouse models have provided information about marker genes and stem cell pathways. Less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed for LGR5 expression by immunohistochemistry. LGR5-positive cells were isolated from 4 adenoma organoid lines and analyzed by RNA-sequencing. LGR5 expression in epithelium and stroma was associated with tumor stage. Integrating functional experiments with RNA-seq data from LGR5-positive adenoma organoid cells and normal colon, we associated expression of CRC-specific genes, including DKK4, with LGR5 expression. This system can be used to study LGR5-expressing cells in human tissue homeostasis and carcinogenesis. ER -