Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network.
Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network.
复制标题
DOI：
10.1016/j.stem.2010.03.016
复制
发表时间：
2010-06-04
期刊：
影响因子：
23.9
通讯作者：
Bernstein BE
中科院分区：
文献类型：
--
作者：
Aiden AP;Rivera MN;Rheinbay E;Ku M;Coffman EJ;Truong TT;Vargas SO;Lander ES;Haber DA;Bernstein BE
肾母细胞瘤是最常见的小儿肾癌。为了确定驱动这种疾病的转录和表观遗传机制，我们比较了肾母细胞瘤，胚胎干细胞（ES）和正常肾脏的全基因组染色质谱。肾母细胞瘤突出地表现出以前在ES细胞中观察到的大的活性染色质结构域。在癌症中，这些结构域通常对应于对肾脏发育至关重要并在肾干细胞隔室中表达的基因。Wilms细胞也表达“胚胎”染色质调节因子，并维持干细胞样p16沉默。最后，Wilms和ES细胞都在沉默启动子处表现出“二价”染色质修饰，这些沉默启动子可能准备激活。在肾母细胞瘤中，二价启动子与特定肾区室中表达的基因相关，并指向在早期祖细胞阶段停滞的肾特异性分化程序。我们认为，肾母细胞与正常肾干细胞共享转录和表观遗传景观，这是固有的易受转化，并可能代表这种疾病的起源细胞。
Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genomewide chromatin profiles of Wilms tumors, embryonic stem (ES) cells and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ES cells. In the cancer, these domains frequently correspond to genes that are critical for kidney development and expressed in the renal stem cell compartment. Wilms cells also express ‘embryonic’ chromatin regulators and maintain stem cell-like p16 silencing. Finally, Wilms and ES cells both exhibit ‘bivalent’ chromatin modifications at silent promoters that may be poised for activation. In Wilms tumor, bivalent promoters correlate to genes expressed in specific kidney compartments and point to a kidney-specific differentiation program arrested at an early-progenitor stage. We suggest that Wilms cells share a transcriptional and epigenetic landscape with a normal renal stem cell, which is inherently susceptible to transformation and may represent a cell-of-origin for this disease.
登录
查看更多内容
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
64.5
作者：
KREIDBERG, JA;SARIOLA, H;JAENISCH, R
通讯作者：
JAENISCH, R
影响因子：
64.5
作者：
CALL, KM;GLASER, T;HOUSMAN, DE
通讯作者：
HOUSMAN, DE
影响因子：
30.8
作者：
BARDEESY, N;FALKOFF, D;PELLETIER, J
通讯作者：
PELLETIER, J
影响因子：
64.8
作者：
通讯作者：
--