PT - JOURNAL ARTICLE 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 R. Hill AU - Alyssa J. Miller AU - Yu-Hwai Tsai 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 TI - Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells AID - 10.1101/118034 DP - 2017 Jan 01 TA - bioRxiv PG - 118034 4099 - http://biorxiv.org/content/early/2017/10/11/118034.short 4100 - http://biorxiv.org/content/early/2017/10/11/118034.full AB - The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while 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 by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from 4 adenoma organoid lines and were subjected to RNA-sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA-seq data from adenoma and normal organoids, we found correlations between LGR5 and CRC- specific genes, including DKK4 (dickkopf WNT signaling pathway inhibitor 4) and SMOC2 (SPARC related modular calcium binding 2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.