Krt19(+)/Lgr5(-) Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine.
Krt19(+)/Lgr5(-) Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine.
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DOI：
10.1016/j.stem.2015.04.013
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发表时间：
2015-06-04
期刊：
影响因子：
23.9
通讯作者：
Wang, Timothy C.
中科院分区：
文献类型：
--
作者：
Asfaha, Samuel;Hayakawa, Yoku;Muley, Ashlesha;Stokes, Sarah;Graham, Trevor A.;Ericksen, Russell E.;Westphalen, Christoph B.;von Burstin, Johannes;Mastracci, Teresa L.;Worthley, Daniel L.;Guha, Chandhan;Quante, Michael;Rustgi, Anil K.;Wang, Timothy C.
The colonic and intestinal epithelium are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt based columnar (CBC) Lgr5+ cells, while the second is comprised of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5-negative stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament, keratin-19 (Krt19), marks long-lived, radiation resistant cells above the crypt base that generate Lgr5+ CBCs in the colon and intestine. In colorectal cancer models, Krt19+ cancer initiating cells are also radioresistant while Lgr5+ stem cells are radiosensitive. Moreover, Lgr5+ stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5+ stem cells results in their regeneration from Krt19 expressing cells. Thus, Krt19+ stem cells are a discrete target relevant for cancer therapy.
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影响因子：
30.8
作者：
Sangiorgi, Eugenio;Capecchi, Mario R.
通讯作者：
Capecchi, Mario R.
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.8
作者：
Seshagiri, Somasekar;Stawiski, Eric W.;Durinck, Steffen;Modrusan, Zora;Storm, Elaine E.;Conboy, Caitlin B.;Chaudhuri, Subhra;Guan, Yinghui;Janakiraman, Vasantharajan;Jaiswal, Bijay S.;Guillory, Joseph;Ha, Connie;Dijkgraaf, Gerrit J. P.;Stinson, Jeremy;Gnad, Florian;Huntley, Melanie A.;Degenhardt, Jeremiah D.;Haverty, Peter M.;Bourgon, Richard;Wang, Weiru;Koeppen, Hartmut;Gentleman, Robert;Starr, Timothy K.;Zhang, Zemin;Largaespada, David A.;Wu, Thomas D.;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
影响因子：
64.5
作者：
Powell AE;Wang Y;Li Y;Poulin EJ;Means AL;Washington MK;Higginbotham JN;Juchheim A;Prasad N;Levy SE;Guo Y;Shyr Y;Aronow BJ;Haigis KM;Franklin JL;Coffey RJ
通讯作者：
Coffey RJ
影响因子：
1.5
作者：
Means, Anna L.;Xu, Yanwen;Gu, Guoqiang
通讯作者：
Gu, Guoqiang