Wilms Tumor Chromatin Profiles Highlight Stem Cell Properties and a Renal Developmental Network

被引：66

作者：

Aiden, Aviva Presser ^{[1
,2
]}

Rivera, Miguel N. ^{[1
,3
,4
,5
,7
]}

Rheinbay, Esther ^{[1
,3
,4
,5
,6
,7
,8
,9
]}

Ku, Manching ^{[1
,3
,4
,5
,6
,7
]}

Coffman, Erik J. ^{[5
,7
]}

Truong, Thanh T. ^{[1
,3
,4
,5
,6
,7
]}

Vargas, Sara O. ^{[10
,11
]}

Lander, Eric S. ^{[1
,12
]}

Haber, Daniel A. ^{[1
,5
,7
]}

Bernstein, Bradley E. ^{[1
,3
,4
,5
,6
,7
]}

机构：

[1] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[2] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[3] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[6] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[7] Boston Univ, Howard Hughes Med Inst, Boston, MA 02115 USA

[8] Boston Univ, Bioinformat Program, Boston, MA 02115 USA

[9] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA

[10] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Boston, MA 02115 USA

[12] MIT, Dept Biol, Cambridge, MA 02142 USA

来源：

CELL STEM CELL | 2010年 / 6卷 / 06期

关键词：

WOLF-HIRSCHHORN-SYNDROME; MICE LACKING GDNF; GENE-EXPRESSION; KIDNEY DEVELOPMENT; HUMAN CANCER; MAMMALIAN KIDNEY; NONCODING RNAS; GENOME; METHYLATION; LOCUS;

D O I：

10.1016/j.stem.2010.03.016

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genome-wide chromatin profiles of Wilms tumors, embryonic stem cells (ESCs), and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ESCs. 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 ESCs 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.

引用

页码：591 / 602

页数：12

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