Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

Meritxell Huch; Paola Bonfanti; Sylvia F. Boj; Toshiro Sato; Cindy J.M. Loomans; Marc Van De Wetering; Mozhdeh Sojoodi; Vivian S.W. Li; Jurian Schuijers; Ana Gracanin; Femke Ringnalda; Harry Begthel; Karien Hamer; Joyce Mulder; Johan H. Van Es; Eelco De Koning; Robert G.J. Vries; Harry Heimberg; Hans Clevers

doi:10.1038/emboj.2013.204

Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

Meritxell Huch, Paola Bonfanti, Sylvia F. Boj, Toshiro Sato, Cindy J.M. Loomans, Marc Van De Wetering, Mozhdeh Sojoodi, Vivian S.W. Li, Jurian Schuijers, Ana Gracanin, Femke Ringnalda, Harry Begthel, Karien Hamer, Joyce Mulder, Johan H. Van Es, Eelco De Koning, Robert G.J. Vries, Harry Heimberg, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

539 Citaten (Scopus)

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Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5 + stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.

Originele taal-2	Engels
Pagina's (van-tot)	2708-2721
Aantal pagina's	14
Tijdschrift	EMBO Journal
Volume	32
Nummer van het tijdschrift	20
DOI's	https://doi.org/10.1038/emboj.2013.204
Status	Gepubliceerd - 16 okt. 2013
Extern gepubliceerd	Ja

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10.1038/emboj.2013.204

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Huch, M., Bonfanti, P., Boj, S. F., Sato, T., Loomans, C. J. M., Van De Wetering, M., Sojoodi, M., Li, V. S. W., Schuijers, J., Gracanin, A., Ringnalda, F., Begthel, H., Hamer, K., Mulder, J., Van Es, J. H., De Koning, E., Vries, R. G. J., Heimberg, H., & Clevers, H. (2013). Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO Journal, 32(20), 2708-2721. https://doi.org/10.1038/emboj.2013.204

@article{ef2ab1f1e1b04559b1a822bfa7ed82dc,

title = "Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis",

abstract = "Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5 + stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.",

keywords = "beta cell, duct cell, pancreas, stem cell, Wnt",

author = "Meritxell Huch and Paola Bonfanti and Boj, {Sylvia F.} and Toshiro Sato and Loomans, {Cindy J.M.} and {Van De Wetering}, Marc and Mozhdeh Sojoodi and Li, {Vivian S.W.} and Jurian Schuijers and Ana Gracanin and Femke Ringnalda and Harry Begthel and Karien Hamer and Joyce Mulder and {Van Es}, {Johan H.} and {De Koning}, Eelco and Vries, {Robert G.J.} and Harry Heimberg and Hans Clevers",

year = "2013",

month = oct,

day = "16",

doi = "10.1038/emboj.2013.204",

language = "English",

volume = "32",

pages = "2708--2721",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

number = "20",

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Huch, M, Bonfanti, P, Boj, SF, Sato, T, Loomans, CJM, Van De Wetering, M, Sojoodi, M, Li, VSW, Schuijers, J, Gracanin, A, Ringnalda, F, Begthel, H, Hamer, K, Mulder, J, Van Es, JH, De Koning, E, Vries, RGJ, Heimberg, H & Clevers, H 2013, 'Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis', EMBO Journal, vol. 32, nr. 20, blz. 2708-2721. https://doi.org/10.1038/emboj.2013.204

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T1 - Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

AU - Huch, Meritxell

AU - Bonfanti, Paola

AU - Boj, Sylvia F.

AU - Sato, Toshiro

AU - Loomans, Cindy J.M.

AU - Van De Wetering, Marc

AU - Sojoodi, Mozhdeh

AU - Li, Vivian S.W.

AU - Schuijers, Jurian

AU - Gracanin, Ana

AU - Ringnalda, Femke

AU - Begthel, Harry

AU - Hamer, Karien

AU - Mulder, Joyce

AU - Van Es, Johan H.

AU - De Koning, Eelco

AU - Vries, Robert G.J.

AU - Heimberg, Harry

AU - Clevers, Hans

PY - 2013/10/16

Y1 - 2013/10/16

N2 - Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5 + stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.

AB - Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5 + stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.

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KW - duct cell

KW - pancreas

KW - stem cell

KW - Wnt

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U2 - 10.1038/emboj.2013.204

DO - 10.1038/emboj.2013.204

M3 - Article

C2 - 24045232

AN - SCOPUS:84885846800

SN - 0261-4189

VL - 32

SP - 2708

EP - 2721

JO - EMBO Journal

JF - EMBO Journal

IS - 20

ER -

Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis

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