Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

Koen C. Oost; Lisa van Voorthuijsen; Arianna Fumagalli; Rik G.H. Lindeboom; Joep Sprangers; Manja Omerzu; Maria J. Rodriguez-Colman; Maria C. Heinz; Ingrid Verlaan-Klink; Madelon M. Maurice; Boudewijn M.T. Burgering; Jacco van Rheenen; Michiel Vermeulen; Hugo J.G. Snippert

doi:10.1016/j.celrep.2018.01.033

Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

Koen C. Oost, Lisa van Voorthuijsen, Arianna Fumagalli, Rik G.H. Lindeboom, Joep Sprangers, Manja Omerzu, Maria J. Rodriguez-Colman, Maria C. Heinz, Ingrid Verlaan-Klink, Madelon M. Maurice, Boudewijn M.T. Burgering, Jacco van Rheenen, Michiel Vermeulen, Hugo J.G. Snippert

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

21 Citaten (Scopus)

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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. Oost et al. present an ASCL2-responsive minigene (STAR) that enables stem cell labeling in patient-derived colorectal cancer organoids, as well as in normal and benign colorectal tumor samples. The user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research into human adult stem cell biology.

Originele taal-2	Engels
Pagina's (van-tot)	1600-1614
Aantal pagina's	15
Tijdschrift	Cell Reports
Volume	22
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1016/j.celrep.2018.01.033
Status	Gepubliceerd - 6 feb. 2018
Extern gepubliceerd	Ja

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Oost, K. C., van Voorthuijsen, L., Fumagalli, A., Lindeboom, R. G. H., Sprangers, J., Omerzu, M., Rodriguez-Colman, M. J., Heinz, M. C., Verlaan-Klink, I., Maurice, M. M., Burgering, B. M. T., van Rheenen, J., Vermeulen, M., & Snippert, H. J. G. (2018). Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene. Cell Reports, 22(6), 1600-1614. https://doi.org/10.1016/j.celrep.2018.01.033

@article{7676c5102c0b4de5b2cf4a8eeb2b15bf,

title = "Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene",

abstract = " 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. Oost et al. present an ASCL2-responsive minigene (STAR) that enables stem cell labeling in patient-derived colorectal cancer organoids, as well as in normal and benign colorectal tumor samples. The user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research into human adult stem cell biology.",

keywords = "ASCL2, colorectal cancer, intestine, LGR5, organoids, stem cells",

author = "Oost, {Koen C.} and {van Voorthuijsen}, Lisa and Arianna Fumagalli and Lindeboom, {Rik G.H.} and Joep Sprangers and Manja Omerzu and Rodriguez-Colman, {Maria J.} and Heinz, {Maria C.} and Ingrid Verlaan-Klink and Maurice, {Madelon M.} and Burgering, {Boudewijn M.T.} and {van Rheenen}, Jacco and Michiel Vermeulen and Snippert, {Hugo J.G.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = feb,

day = "6",

doi = "10.1016/j.celrep.2018.01.033",

language = "English",

volume = "22",

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Oost, KC, van Voorthuijsen, L, Fumagalli, A, Lindeboom, RGH, Sprangers, J, Omerzu, M, Rodriguez-Colman, MJ, Heinz, MC, Verlaan-Klink, I, Maurice, MM, Burgering, BMT, van Rheenen, J, Vermeulen, M & Snippert, HJG 2018, 'Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene', Cell Reports, vol. 22, nr. 6, blz. 1600-1614. https://doi.org/10.1016/j.celrep.2018.01.033

TY - JOUR

T1 - Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

AU - Oost, Koen C.

AU - van Voorthuijsen, Lisa

AU - Fumagalli, Arianna

AU - Lindeboom, Rik G.H.

AU - Sprangers, Joep

AU - Omerzu, Manja

AU - Rodriguez-Colman, Maria J.

AU - Heinz, Maria C.

AU - Verlaan-Klink, Ingrid

AU - Maurice, Madelon M.

AU - Burgering, Boudewijn M.T.

AU - van Rheenen, Jacco

AU - Vermeulen, Michiel

AU - Snippert, Hugo J.G.

PY - 2018/2/6

Y1 - 2018/2/6

N2 - 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. Oost et al. present an ASCL2-responsive minigene (STAR) that enables stem cell labeling in patient-derived colorectal cancer organoids, as well as in normal and benign colorectal tumor samples. The user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research into human adult stem cell biology.

AB - 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. Oost et al. present an ASCL2-responsive minigene (STAR) that enables stem cell labeling in patient-derived colorectal cancer organoids, as well as in normal and benign colorectal tumor samples. The user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research into human adult stem cell biology.

KW - ASCL2

KW - colorectal cancer

KW - intestine

KW - LGR5

KW - organoids

KW - stem cells

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U2 - 10.1016/j.celrep.2018.01.033

DO - 10.1016/j.celrep.2018.01.033

M3 - Article

C2 - 29425513

AN - SCOPUS:85041715828

SN - 2211-1247

VL - 22

SP - 1600

EP - 1614

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

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