Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci

被引：103

作者：

Zacharek, Sima J. ^{[1
,3
,5
]}

Fillmore, Christine M. ^{[1
,3
,5
]}

Lau, Allison N. ^{[1
,3
,5
]}

Gludish, David W. ^{[1
,3
,5
]}

Chou, Alan ^{[1
,3
,5
]}

Ho, Joshua W. K. ^{[4
,6
]}

Zamponi, Raffaella ^{[1
,3
,5
]}

Gazit, Roi ^{[2
,5
]}

Bock, Christoph ^{[5
,7
,8
,9
]}

Jaeger, Natalie ^{[5
,7
,8
]}

Smith, Zachary D. ^{[5
,7
,8
]}

Kim, Tae-min ^{[4
]}

Saunders, Arven H. ^{[1
,3
,5
]}

Wong, Janice ^{[1
,3
,5
]}

Lee, Joo-Hyeon ^{[1
,3
,5
]}

Roach, Rebecca R. ^{[1
,3
,5
]}

Rossi, Derrick J. ^{[2
,5
,8
]}

Meissner, Alex ^{[5
,7
,8
]}

Gimelbrant, Alexander A. ^{[3
,10
]}

Park, Peter J. ^{[4
,6
]}

Kim, Carla F. ^{[1
,3
,5
]}

机构：

[1] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[2] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA

[5] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[6] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[7] Broad Inst, Cambridge, MA 02142 USA

[8] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[9] Max Planck Inst Informat, D-66123 Saarbrucken, Germany

[10] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2011年 / 9卷 / 03期

关键词：

P57(KIP2);

D O I：

10.1016/j.stem.2011.07.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

BMI1 is required for the self-renewal of stem cells in many tissues including the lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes, which exhibit expression from only the maternally or paternally inherited allele, are known to regulate developmental processes, but what their role is in adult cells remains a fundamental question. Many imprinted genes were derepressed in Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression of p57 and other imprinted genes was required for lung cell self-renewal in culture and correlated with repair of lung epithelial cell injury in vivo. Our data suggest that BM11-dependent regulation of expressed alleles at imprinted loci, distinct from imprinting per se, is required for control of lung stem cells. We anticipate that the regulation and function of imprinted genes is crucial for self-renewal in diverse adult tissue-specific stem cells.

引用

页码：272 / 280

页数：9

共 5 条

[1] The mammalian epigenome [J].