Dissecting self-renewal in stem cells with RNA interference

被引：794

作者：

Ivanova, Natalia ^{[1
]}

Dobrin, Radu ^{[1
]}

Lu, Rong ^{[1
]}

Kotenko, Iulia ^{[1
]}

Levorse, John ^{[1
]}

DeCoste, Christina ^{[1
]}

Schafer, Xenia ^{[1
]}

Lun, Yi ^{[1
]}

Lemischka, Ihor R. ^{[1
]}

机构：

[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

来源：

NATURE | 2006年 / 442卷 / 7102期

关键词：

D O I：

10.1038/nature04915

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

We present an integrated approach to identify genetic mechanisms that control self-renewal in mouse embryonic stem cells. We use short hairpin RNA (shRNA) loss-of-function techniques to downregulate a set of gene products whose expression patterns suggest self-renewal regulatory functions. We focus on transcriptional regulators and identify seven genes for which shRNA-mediated depletion negatively affects self-renewal, including four genes with previously unrecognized roles in self-renewal. Perturbations of these gene products are combined with dynamic, global analyses of gene expression. Our studies suggest specific biological roles for these molecules and reveal the complexity of cell fate regulation in embryonic stem cells.

引用

页码：533 / 538

页数：6

共 37 条

[1]

Multipotent cell lineages in early mouse development depend on SOX2 function [J].

Avilion, AA ;

Nicolis, SK ;

Pevny, LH ;

Perez, L ;

Vivian, N ;

Lovell-Badge, R .

GENES & DEVELOPMENT, 2003, 17 (01) :126-140

[2]

Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome [J].

Bamshad, M ;

Lin, RC ;

Law, DJ ;

Watkins, WS ;

Krakowiak, PA ;

Moore, ME ;

Franceschini, P ;

Lala, R ;

Holmes, LB ;

Gebuhr, TC ;

Bruneau, BG ;

Schinzel, A ;

Seidman, JG ;

Seidman, CE ;

Jorde, LB .

NATURE GENETICS, 1997, 16 (03) :311-315

[3]

A large-scale RNAi screen in human cells identifies new components of the p53 pathway [J].

Berns, K ;

Hijmans, EM ;

Mullenders, J ;

Brummelkamp, TR ;

Velds, A ;

Heimerikx, M ;

Kerkhoven, RM ;

Madiredjo, M ;

Nijkamp, W ;

Weigelt, B ;

Agami, R ;

Ge, W ;

Cavet, G ;

Linsley, PS ;

Beijersbergen, RL ;

Bernards, R .

NATURE, 2004, 428 (6981) :431-437

[4]

Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei [J].

Bortvin, A ;

Eggan, K ;

Skaletsky, H ;

Akutsu, H ;

Berry, DL ;

Yanagimachi, R ;

Page, DC ;

Jaenisch, R .

DEVELOPMENT, 2003, 130 (08) :1673-1680

[5]

Core transcriptional regulatory circuitry in human embryonic stem cells [J].

Boyer, LA ;

Lee, TI ;

Cole, MF ;

Johnstone, SE ;

Levine, SS ;

Zucker, JR ;

Guenther, MG ;

Kumar, RM ;

Murray, HL ;

Jenner, RG ;

Gifford, DK ;

Melton, DA ;

Jaenisch, R ;

Young, RA .

CELL, 2005, 122 (06) :947-956

[6]

Signalling, cell cycle and pluripotency in embryonic stem cells [J].

Burdon, T ;

Smith, A ;

Savatier, P .

TRENDS IN CELL BIOLOGY, 2002, 12 (09) :432-438

[7]

Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells [J].

Burdon, T ;

Stracey, C ;

Chambers, I ;

Nichols, J ;

Smith, A .

DEVELOPMENTAL BIOLOGY, 1999, 210 (01) :30-43

[8]

Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells [J].

Chambers, I ;

Colby, D ;

Robertson, M ;

Nichols, J ;

Lee, S ;

Tweedie, S ;

Smith, A .

CELL, 2003, 113 (05) :643-655

[9]

Spatial and temporal patterns of ERK signaling during mouse embryogenesis [J].

Corson, LB ;

Yamanaka, Y ;

Lai, KMV ;

Rossant, J .

DEVELOPMENT, 2003, 130 (19) :4527-4537

[10]

Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome [J].

Davenport, TG ;

Jerome-Majewska, LA ;

Papaioannou, VE .

DEVELOPMENT, 2003, 130 (10) :2263-2273

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