The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.
The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.
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DOI：
10.1016/j.cell.2012.02.042
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发表时间：
2012-03-30
期刊：
影响因子：
64.5
通讯作者：
Coffey RJ
中科院分区：
文献类型：
--
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
谱系作图已经确定了增殖和静止的肠干细胞，但控制干细胞静止的分子电路还不完全清楚。通过谱系映射，我们发现Lrig 1是一种泛ErbB抑制剂，主要标记位于隐窝基底的非循环、长寿命干细胞，这些干细胞在损伤后增殖和分裂以补充受损的隐窝。Lrig 1+结肠干细胞的转录组谱显著不同于高度增殖的Lgr 5+结肠干细胞; Lrig 1+群体中上调的基因包括参与细胞周期抑制和对氧化损伤的反应的基因。Lrig 1+细胞中Apc的缺失导致肠腺瘤，Lrig 1的基因切除导致ErbB 1 -3表达升高和十二指肠腺瘤。这些结果揭示了增殖和静止的肠干细胞之间的关系，并支持一个模型，其中肠干细胞的静止是由校准的ErbB信号转导与负调节因子的损失，易患肿瘤。
Lineage mapping has identified both proliferative and quiescent intestinal stem cells, but the molecular circuitry controlling stem cell quiescence is incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor, marks predominately non-cycling, long-lived stem cells located at the crypt base that, upon injury, proliferate and divide to replenish damaged crypts. Transcriptome profiling of Lrig1+ colonic stem cells differs markedly from highly proliferative, Lgr5+ colonic stem cells; genes up-regulated in the Lrig1+ population include those involved in cell cycle repression and response to oxidative damage. Loss of Apc in Lrig1+ cells leads to intestinal adenomas and genetic ablation of Lrig1 results in heightened ErbB1-3 expression and duodenal adenomas. These results shed light on the relationship between proliferative and quiescent intestinal stem cells, and support a model in which intestinal stem cell quiescence is maintained by calibrated ErbB signaling with loss of a negative regulator predisposing to neoplasia.
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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：
11.2
作者：
Miller, Jamie K.;Shattuck, David L.;Ingalla, Ellen Q.;Yen, Lily;Borowsky, Alexander D.;Young, Lawrence J. T.;Cardiff, Robert D.;Carraway, Kermit L., III;Sweeney, Colleen
通讯作者：
Sweeney, Colleen
影响因子：
3.1
作者：
Ljuslinder, Ingrid;Golovleva, Irina;Malmer, Beatrice
通讯作者：
Malmer, Beatrice
影响因子：
16.6
作者：
Escobar, Marion;Nicolas, Pierre;Sangar, Fatiha;Laurent-Chabalier, Sabine;Clair, Philippe;Joubert, Dominique;Jay, Philippe;Legraverend, Catherine
通讯作者：
Legraverend, Catherine
DOI：
10.1073/pnas.1013004108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Montgomery, Robert K.;Carlone, Diana L.;Breault, David T.
通讯作者：
Breault, David T.