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Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene
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 limi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847189/ https://www.ncbi.nlm.nih.gov/pubmed/29425513 http://dx.doi.org/10.1016/j.celrep.2018.01.033 |
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author | Oost, Koen C. van Voorthuijsen, Lisa Fumagalli, Arianna Lindeboom, Rik G.H. Sprangers, Joep Omerzu, Manja Rodriguez-Colman, Maria J. Heinz, Maria C. Verlaan-Klink, Ingrid Maurice, Madelon M. Burgering, Boudewijn M.T. van Rheenen, Jacco Vermeulen, Michiel Snippert, Hugo J.G. |
author_facet | Oost, Koen C. van Voorthuijsen, Lisa Fumagalli, Arianna Lindeboom, Rik G.H. Sprangers, Joep Omerzu, Manja Rodriguez-Colman, Maria J. Heinz, Maria C. Verlaan-Klink, Ingrid Maurice, Madelon M. Burgering, Boudewijn M.T. van Rheenen, Jacco Vermeulen, Michiel Snippert, Hugo J.G. |
author_sort | Oost, Koen C. |
collection | PubMed |
description | 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 activity of ASCL2, a master regulator of LGR5(+) intestinal stem cells. Using lentiviral infection, STAR drives specific expression in stem cells of normal organoids and in multiple engineered and patient-derived CRC organoids of different genetic makeup. STAR reveals that differentiation hierarchies and the potential for cell fate plasticity are present at all stages of human CRC development. Organoid technology, in combination with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. |
format | Online Article Text |
id | pubmed-5847189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58471892018-03-13 Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene Oost, Koen C. van Voorthuijsen, Lisa Fumagalli, Arianna Lindeboom, Rik G.H. Sprangers, Joep Omerzu, Manja Rodriguez-Colman, Maria J. Heinz, Maria C. Verlaan-Klink, Ingrid Maurice, Madelon M. Burgering, Boudewijn M.T. van Rheenen, Jacco Vermeulen, Michiel Snippert, Hugo J.G. Cell Rep Article 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 activity of ASCL2, a master regulator of LGR5(+) intestinal stem cells. Using lentiviral infection, STAR drives specific expression in stem cells of normal organoids and in multiple engineered and patient-derived CRC organoids of different genetic makeup. STAR reveals that differentiation hierarchies and the potential for cell fate plasticity are present at all stages of human CRC development. Organoid technology, in combination with the user-friendly nature of STAR, will facilitate basic research into human adult stem cell biology. Cell Press 2018-02-08 /pmc/articles/PMC5847189/ /pubmed/29425513 http://dx.doi.org/10.1016/j.celrep.2018.01.033 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Oost, Koen C. van Voorthuijsen, Lisa Fumagalli, Arianna Lindeboom, Rik G.H. Sprangers, Joep Omerzu, Manja Rodriguez-Colman, Maria J. Heinz, Maria C. Verlaan-Klink, Ingrid Maurice, Madelon M. Burgering, Boudewijn M.T. van Rheenen, Jacco Vermeulen, Michiel Snippert, Hugo J.G. Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title | Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title_full | Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title_fullStr | Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title_full_unstemmed | Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title_short | Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene |
title_sort | specific labeling of stem cell activity in human colorectal organoids using an ascl2-responsive minigene |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847189/ https://www.ncbi.nlm.nih.gov/pubmed/29425513 http://dx.doi.org/10.1016/j.celrep.2018.01.033 |
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