RT Journal Article SR Electronic T1 Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 118034 DO 10.1101/118034 A1 Michael K. Dame A1 Durga Attili A1 Shannon D. McClintock A1 Priya H. Dedhia A1 Peter Ouilette A1 Olaf Hardt A1 Alana M Chin A1 Xiang Xue A1 Julie Laliberte A1 Erica L Katz A1 Gina M Newsome A1 David Hill A1 Alyssa Miller A1 David Agorku A1 Christopher H Altheim A1 Andreas Bosio A1 Becky Simon A1 Linda C Samuelson A1 Jay A Stoerker A1 Henry D Appelman A1 James Varani A1 Max S. Wicha A1 Dean E. Brenner A1 Yatrik M. Shah A1 Jason R Spence A1 Justin A. Colacino YR 2017 UL http://biorxiv.org/content/early/2017/03/18/118034.abstract AB 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.