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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
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.
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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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