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Title: A genome editing approach to study cancer stem cells in human tumors
Author: Cortina, Carme
Turon, Gemma
Stork, Diana
Hernando Momblona, Xavier
Sevillano, Marta
Aguilera, Mònica
Tosi, Sébastien
Merlos Suárez, Anna
Stephan-Otto Attolini, Camille
Sancho, Elena
Batlle, Eduard
Keywords: Cèl·lules mare
Càncer colorectal
Stem cells
Colorectal cancer
Issue Date: 3-May-2017
Publisher: European Molecular Biology Organization
Abstract: The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient-derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage-tracing cassettes knocked in the LGR5 locus. Analysis of LGR5-EGFP+ cells isolated from organoid-derived xenografts demonstrated that these cells express a gene program similar to that of normal intestinal stem cells and that they propagate the disease to recipient mice very efficiently. Lineage-tracing experiments showed that LGR5+ CRC cells self-renew and generate progeny over long time periods that undergo differentiation toward mucosecreting- and absorptive-like phenotypes. These genetic experiments confirm that human CRCs adopt a hierarchical organization reminiscent of that of the normal colonic epithelium. The strategy described herein may have broad applications to study cell heterogeneity in human tumors.
Note: Reproducció del document publicat a:
It is part of: EMBO Molecular Medicine, 2017, num. 9, p. 869-879
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ISSN: 1757-4676
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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