Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis.
Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis.
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DOI：
10.1038/emboj.2013.204
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发表时间：
2013-10-16
期刊：
影响因子：
11.4
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Huch, Meritxell;Bonfanti, Paola;Boj, Sylvia F.;Sato, Toshiro;Loomans, Cindy J. M.;van de Wetering, Marc;Sojoodi, Mozhdeh;Li, Vivian S. W.;Schuijers, Jurian;Gracanin, Ana;Ringnalda, Femke;Begthel, Harry;Hamer, Karien;Mulder, Joyce;van Es, Johan H.;de Koning, Eelco;Vries, Robert G. J.;Heimberg, Harry;Clevers, Hans
LGR5标记多个成体器官中的成体干细胞，是WNT激动型R-海绵蛋白(RSPO)的受体。肠道、胃和肝脏的Lgr5+干细胞在3D培养中生长，形成不断膨胀的有机类物质，类似于起源的组织。在成人胰腺中，WNT信号不活跃，Lgr5在生理条件下不表达。然而，我们现在报道，在部分胰管结扎(PDL)损伤后，Wnt通路被强烈激活，伴随着Lgr5在再生胰管中的表达。在体外，小鼠胰腺的导管碎片在以Rspo1为基础的培养物中启动Lgr5的表达，并发育成萌芽的囊状结构(器官样)，在40周内每周扩大5倍。单个分离的导管细胞也可以培养成胰腺类器官，其中包含可以克隆扩增的Lgr5干/祖细胞。克隆类胰腺器官在移植后可被诱导分化为导管细胞和内分泌细胞，从而证明其具有双重潜能。
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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影响因子：
13.5
作者：
Dorrell, Craig;Erker, Laura;Lanxon-Cookson, Kelsea M.;Abraham, Stephanie L.;Victoroff, Tristan;Ro, Simon;Canaday, Pamela S.;Streeter, Philip R.;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Pasca di Magliano M;Biankin AV;Heiser PW;Cano DA;Gutierrez PJ;Deramaudt T;Segara D;Dawson AC;Kench JG;Henshall SM;Sutherland RL;Dlugosz A;Rustgi AK;Hebrok M
通讯作者：
Hebrok M
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
DOI：
10.1073/pnas.97.14.7999
发表时间：
2000-07-05
影响因子：
11.1
作者：
Bonner-Weir, S;Taneja, M;O'Neil, JJ
通讯作者：
O'Neil, JJ