Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.
Bmi1 marks distinct castration-resistant luminal progenitor cells competent for prostate regeneration and tumour initiation.
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DOI：
10.1038/ncomms12943
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发表时间：
2016-10-05
影响因子：
16.6
通讯作者：
Abdulkadir, Sarki A.
中科院分区：
文献类型：
--
作者：
Yoo, Young A.;Roh, Meejeon;Naseem, Anum F.;Lysy, Barbara;Desouki, Mohamed M.;Unno, Kenji;Abdulkadir, Sarki A.
确定具有干/祖细胞特性的细胞群是了解前列腺发育和肿瘤发生的关键。在这里，我们表明，polycomb阻遏蛋白Bmi 1标志着人口的去势抵抗管腔上皮细胞富集在小鼠近端前列腺。我们采用谱系追踪来显示这些去势抗性Bmi 1表达细胞（或CARB）能够进行组织再生和自我更新。值得注意的是，CARB与先前描述的管腔去势抗性Nkx3.1表达细胞（CARN）不同。Pten缺失后，CARB可以作为前列腺癌起源细胞，产生前列腺腔肿瘤。使用R26 R-confetti等位基因的克隆分析表明，从位于近端前列腺的CARB优先肿瘤起始。这些研究将Bmi 1鉴定为在近端前列腺中富集的去势抵抗性管腔上皮细胞的独特群体的标志物，所述细胞可以作为前列腺癌的起源细胞。 多梳阻遏蛋白Bmi 1在自我更新和肿瘤发生中起作用。在这里，作者使用谱系追踪来表明Bmi表达细胞是一个独特的细胞群体，主要存在于管腔区室中，其具有去势抗性，可以引发癌症并再生前列腺。
Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previously described luminal castration-resistant Nkx3.1-expressing cells (CARNs). CARBs can serve as a prostate cancer cell-of-origin upon Pten deletion, yielding luminal prostate tumours. Clonal analysis using the R26R-confetti allele indicates preferential tumour initiation from CARBs localized to the proximal prostate. These studies identify Bmi1 as a marker for a distinct population of castration-resistant luminal epithelial cells enriched in the proximal prostate that can serve as a cell of origin for prostate cancer. The polycomb repressor protein Bmi1 has a role in self-renewal and tumorigenesis. Here, the authors use lineage tracing to show that Bmi-expressing cells are a distinct population of cells, primarily found in the luminal compartment, which is castration resistant, can initiate cancer and regenerate prostate.
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影响因子：
30.8
作者：
Sangiorgi, Eugenio;Capecchi, Mario R.
通讯作者：
Capecchi, Mario R.
DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
DOI：
10.1083/jcb.200202067
发表时间：
2002-06-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tsujimura A;Koikawa Y;Salm S;Takao T;Coetzee S;Moscatelli D;Shapiro E;Lepor H;Sun TT;Wilson EL
通讯作者：
Wilson EL
影响因子：
21.3
作者：
Ousset, Marielle;Van Keymeulen, Alexandra;Blanpain, Cedric
通讯作者：
Blanpain, Cedric
影响因子：
64.5
作者：
Snippert, Hugo J.;van der Flier, Laurens G.;Clevers, Hans
通讯作者：
Clevers, Hans