Proteomics,Multiomics

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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): Orbitrap Fusion

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

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Organoid technology provides the possibility of culturing patient-derived colon tissue and colorectal cancers (CRCs) while maintaining all functional and phenotypic characteristics. Labeling stem cells, especially in normal and benign tumor organoids of human colon, is challenging and therefore limits maximal exploitation of organoid libraries for human stem cell research. Here, we developed STAR (stem cell Ascl2 reporter), a minimal enhancer/promoter element that reports transcriptional activit  ...[more]

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