Specific labeling of stem cell activity in human colorectal organoidsusing an ASCL2-responsive minigene

ABSTRACT: Organoid technology provides the possibility to culture human colontissue and patient-derived colorectal cancers (CRC) while maintainingall functional and phenotypic characteristics. Labeling of human colonstem cells (CoSCs), especially in normal and benign tumor organoids, ischallenging and therefore limits usability of multi-patient organoidlibraries for CoSC research. Here, we developed STAR (STem cell Ascl2Reporter), a minimal enhancer/promoter element that reportstranscriptional activity of ASCL2, a master regulator of LGR5+ CoSCfate. Among others via lentiviral infection, STAR minigene labels stemcells in normal as well as in multiple engineered and patient-derivedCRC organoids of different stage and genetic make-up. STAR revealed thatstem cell driven differentiation hierarchies and the capacity of cellfate plasticity (de-differentiation) are present at all stages of humanCRC development. The flexible and user-friendly nature of STARapplications in combination with organoid technology will facilitatebasic research on human adult stem cell biology.

OTHER RELATED OMICS DATASETS IN: PRJNA387402

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon Epithelial Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Rik Lindeboom  

LAB HEAD: Hugo Snippert

PROVIDER: PXD006575 | Pride | 2018-01-29

REPOSITORIES: pride