Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/110578
A genome editing approach to study cancer stem cells in human tumors
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries
Matèries (anglès)
Citació
Citació
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. A genome editing approach to study cancer stem cells in human tumors. _EMBO Molecular Medicine_. 2017. Vol. 9, núm. 869-879. [consulta: 20 de gener de 2026]. ISSN: 1757-4676. [Disponible a: https://hdl.handle.net/2445/110578]