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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: http://dx.doi.org/10.15252/emmm.201707550 |
It is part of: | EMBO Molecular Medicine, 2017, num. 9, p. 869-879 |
URI: | http://hdl.handle.net/2445/110578 |
Related resource: | http://dx.doi.org/10.15252/emmm.201707550 |
ISSN: | 1757-4676 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Publicacions de projectes de recerca finançats per la UE |
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