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Series GSE111269 Query DataSets for GSE111269
Status Public on Aug 27, 2018
Title A CRISPR loss-of-function Hepatic progenitor cells expansion screen in liver organoids
Organisms Mus musculus; synthetic construct
Experiment type Other
Summary Biliary epithelial cells (BECs) form bile ducts in the liver, and are facultative liver stem cells that establish a ductular reaction (DR) to support liver regeneration following injury. Liver damage induces periportal LGR5+ putative liver stem cells which can form BEC-like organoids, suggesting RSPO-LGR4/5-mediated WNT/β-catenin activity is important for a DR. We addressed the roles for this and other signaling pathways in a DR by performing a focused CRISPR-based loss-of-function screen in BEC-like organoids, followed by in vivo validation and single-cell RNA sequencing. We found BECs lack and do not require LGR4/5-mediated WNT/β-Catenin signaling during DR, while YAP and mTORC1 signaling are required for this process. Upregulation of LGR5/AXIN2 is required in hepatocytes to enable their regenerative capacity in response to injury. Together, these data highlight heterogeneity within the BEC pool and delineate signaling pathways involved.
Overall design The 1000 element library is a pooled CRISPR library with 1000 unique CRISPR sgRNA. The take rate library is a DNA barcode library ( The manuscript presents the finding of a pooled CRISPR screen on liver organoid culture system using a 1000 element CRISPR library. To develop the screening assay, we evaluated the clonal growth kinetics of the liver organoids by infecting the organoids with the take rate library which is composed of DNA barcodes that do not perform genetic perturbation. The take rate library result confirms that the liver organoids do not display strong clonal growth and thus are suitable for screening.
We use cell survival and proliferation as the measure for identifying signalling pathways regulating HPC expansion in vitro.
Contributor(s) Planas-Paz L, Sun T, Pikiolek M, Cochran NR, Bergling S, Orsini V, Yang Z, Sigoillot F, Jetzer J, Syed M, Neri M, Schuierer S, Morelli L, Hoppe PS, Schwarzer W, Cobos CM, Alford JL, Zhang L, Cuttat R, Waldt A, Carballido-Perrig N, Nigsch F, Kinzel B, Nicholson TB, Yang Y, Mao X, Terracciano LM, Russ C, Reece-Hoyes JS, Keller CG, Sailer AW, Bouwmeester T, Greenbaum LE, Lugus JJ, Cong F, McAllister G, Hoffman GR, Roma G, Tchorz JS
Citation(s) 31080135
Submission date Feb 28, 2018
Last update date Jan 13, 2024
Contact name Frederic D Sigoillot
Organization name Novartis Institutes for Biomedical Research
Department Chemical Biology and Therapeutics
Lab Data Science
Street address 181 Massachusetts Avenue
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19604 Illumina HiSeq 2500 (synthetic construct)
Samples (6)
GSM3027634 1000_element_library_plasmid
GSM3027635 1000_element_library_sample_Day12_replicate1
GSM3027636 1000_element_library_sample_Day12_replicate2
BioProject PRJNA436376
SRA SRP133678

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Supplementary file Size Download File type/resource
GSE111269_RAW.tar 196.6 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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