spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 9 Feb 2005
doi: 10.1242/dev.01706

This Article
Right arrow Full Text (PDF)
Right arrowOA All Versions of this Article:
dev.01706v1
132/6/1273    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by James, D.
Right arrow Articles by Hemmati-Brivanlou, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by James, D.
Right arrow Articles by Hemmati-Brivanlou, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research article

TGF{beta}/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells


Daylon James, Ariel J. Levine, Daniel Besser, and Ali Hemmati-Brivanlou*
* Author for correspondence (e-mail: brvnlou{at}mail.rockefeller.edu)

Human embryonic stem cells (hESCs) self-renew indefinitely and give rise to derivatives of all three primary germ layers, yet little is known about the signaling cascades that govern their pluripotent character. Because it plays a prominent role in the early cell fate decisions of embryonic development, we have examined the role of TGF{beta} superfamily signaling in hESCs. We found that, in undifferentiated cells, the TGF{beta}/activin/nodal branch is activated (through the signal transducer SMAD2/3) while the BMP/GDF branch (SMAD1/5) is only active in isolated mitotic cells. Upon early differentiation, SMAD2/3 signaling is decreased while SMAD1/5 signaling is activated. We next tested the functional role of TGF{beta}/activin/nodal signaling in hESCs and found that it is required for the maintenance of markers of the undifferentiated state. We extend these findings to show that SMAD2/3 activation is required downstream of WNT signaling, which we have previously shown to be sufficient to maintain the undifferentiated state of hESCs. Strikingly, we show that in ex vivo mouse blastocyst cultures, SMAD2/3 signaling is also required to maintain the inner cell mass (from which stem cells are derived). These data reveal a crucial role for TGF{beta} signaling in the earliest stages of cell fate determination and demonstrate an interconnection between TGF{beta} and WNT signaling in these contexts.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Cold Spring Harb. Perspect. Biol.Home page
A. F. Schier
Nodal Morphogens
Cold Spring Harb Perspect Biol, November 1, 2009; 1(5): a003459 - a003459.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Di Pasquale and A. H. Brivanlou
Bone Morphogenetic Protein 15 (BMP15) Acts as a BMP and Wnt Inhibitor during Early Embryogenesis
J. Biol. Chem., September 18, 2009; 284(38): 26127 - 26136.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
Y. Xia and A. L Schneyer
The biology of activin: recent advances in structure, regulation and function
J. Endocrinol., July 1, 2009; 202(1): 1 - 12.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
H.-F. Chen, C.-Y. Chuang, Y.-K. Shieh, H.-W. Chang, H.-N. Ho, and H.-C. Kuo
Novel autogenic feeders derived from human embryonic stem cells (hESCs) support an undifferentiated status of hESCs in xeno-free culture conditions
Hum. Reprod., May 1, 2009; 24(5): 1114 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
L. Vallier, S. Mendjan, S. Brown, Z. Chng, A. Teo, L. E. Smithers, M. W. B. Trotter, C. H.-H. Cho, A. Martinez, P. Rugg-Gunn, et al.
Activin/Nodal signalling maintains pluripotency by controlling Nanog expression
Development, April 15, 2009; 136(8): 1339 - 1349.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. L. Swaney, C. D. Wenger, J. A. Thomson, and J. J. Coon
Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry
PNAS, January 27, 2009; 106(4): 995 - 1000.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Wang, Y. Shen, X. Yuan, K. Chen, X. Guo, Y. Chen, Y. Niu, J. Li, R.-H. Xu, X. Yan, et al.
Dissecting Signaling Pathways That Govern Self-renewal of Rabbit Embryonic Stem Cells
J. Biol. Chem., December 19, 2008; 283(51): 35929 - 35940.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Nagaoka, Y. Hagiwara, K. Takemura, Y. Murakami, J. Li, S. A. Duncan, and T. Akaike
Design of the Artificial Acellular Feeder Layer for the Efficient Propagation of Mouse Embryonic Stem Cells
J. Biol. Chem., September 26, 2008; 283(39): 26468 - 26476.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. K. Furue, J. Na, J. P. Jackson, T. Okamoto, M. Jones, D. Baker, R.-I. Hata, H. D. Moore, J. D. Sato, and P. W. Andrews
Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium
PNAS, September 9, 2008; 105(36): 13409 - 13414.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Wu, W. Zhang, G. Chen, L. Cheng, J. Liao, N. Jia, Y. Gao, H. Dai, J. Yuan, L. Cheng, et al.
Combinatorial Signals of Activin/Nodal and Bone Morphogenic Protein Regulate the Early Lineage Segregation of Human Embryonic Stem Cells
J. Biol. Chem., September 5, 2008; 283(36): 24991 - 25002.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
F. Meng, X. Cheng, L. Yang, N. Hou, X. Yang, and A. Meng
Accelerated re-epithelialization in Dpr2-deficient mice is associated with enhanced response to TGF{beta} signaling
J. Cell Sci., September 1, 2008; 121(17): 2904 - 2912.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
T. Sumi, N. Tsuneyoshi, N. Nakatsuji, and H. Suemori
Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/{beta}-catenin, Activin/Nodal and BMP signaling
Development, September 1, 2008; 135(17): 2969 - 2979.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
J. Yu and J. A. Thomson
Pluripotent stem cell lines
Genes & Dev., August 1, 2008; 22(15): 1987 - 1997.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L.-M. Postovit, N. V. Margaryan, E. A. Seftor, D. A. Kirschmann, A. Lipavsky, W. W. Wheaton, D. E. Abbott, R. E. B. Seftor, and M. J. C. Hendrix
Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells
PNAS, March 18, 2008; 105(11): 4329 - 4334.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. C. Zhu, J. Q. Boone, P. A. Jensen, S. Hanna, L. Podemski, J. Locke, C. Q. Doe, and M. B. O'Connor
Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain
Development, February 1, 2008; 135(3): 513 - 521.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Wang, T. C. Schulz, E. S. Sherrer, D. S. Dauphin, S. Shin, A. M. Nelson, C. B. Ware, M. Zhan, C.-Z. Song, X. Chen, et al.
Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling
Blood, December 1, 2007; 110(12): 4111 - 4119.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Bioactive and Compatible PolymersHome page
S. H. Emami and M. A. S. Chaudhry
Self-renewal and Proliferation of Murine Embryonic Stem Cells: A Study of Glycosaminoglycans Effect on Feeder-Free Cultures
Journal of Bioactive and Compatible Polymers, May 1, 2007; 22(3): 314 - 322.
[Abstract] [PDF]

Home page
 DevelopmentHome page
M. M. Shen
Nodal signaling: developmental roles and regulation
Development, March 15, 2007; 134(6): 1023 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
C. Allegrucci and L.E. Young
Differences between human embryonic stem cell lines
Hum. Reprod. Update, March 1, 2007; 13(2): 103 - 120.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
K. Ogawa, A. Saito, H. Matsui, H. Suzuki, S. Ohtsuka, D. Shimosato, Y. Morishita, T. Watabe, H. Niwa, and K. Miyazono
Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells
J. Cell Sci., January 1, 2007; 120(1): 55 - 65.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. B. Steiner, M. J. Engleka, Q. Lu, E. C. Piwarzyk, S. Yaklichkin, J. L. Lefebvre, J. W. Walters, L. Pineda-Salgado, P. A. Labosky, and D. S. Kessler
FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development
Development, December 15, 2006; 133(24): 4827 - 4838.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Nakatake, N. Fukui, Y. Iwamatsu, S. Masui, K. Takahashi, R. Yagi, K. Yagi, J.-i. Miyazaki, R. Matoba, M. S. H. Ko, et al.
Klf4 Cooperates with Oct3/4 and Sox2 To Activate the Lefty1 Core Promoter in Embryonic Stem Cells
Mol. Cell. Biol., October 15, 2006; 26(20): 7772 - 7782.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
M. Bibikova, E. Chudin, B. Wu, L. Zhou, E. W. Garcia, Y. Liu, S. Shin, T. W. Plaia, J. M. Auerbach, D. E. Arking, et al.
Human embryonic stem cells have a unique epigenetic signature
Genome Res., September 1, 2006; 16(9): 1075 - 1083.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
S.-y. Yasuda, N. Tsuneyoshi, T. Sumi, K. Hasegawa, T. Tada, N. Nakatsuji, and H. Suemori
NANOG maintains self-renewal of primate ES cells in the absence of a feeder layer.
Genes Cells, September 1, 2006; 11(9): 1115 - 1123.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Knockaert, G. Sapkota, C. Alarcon, J. Massague, and A. H. Brivanlou
Unique players in the BMP pathway: Small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling
PNAS, August 8, 2006; 103(32): 11940 - 11945.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. Mesnard, M. Guzman-Ayala, and D. B. Constam
Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning
Development, July 1, 2006; 133(13): 2497 - 2505.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Yao, S. Chen, J. Clark, E. Hao, G. M. Beattie, A. Hayek, and S. Ding
Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions
PNAS, May 2, 2006; 103(18): 6907 - 6912.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
Y.-G. Chen, Q. Wang, S.-L. Lin, C. D. Chang, J. Chung, and S.-Y. Ying
Activin Signaling and Its Role in Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis.
Experimental Biology and Medicine, May 1, 2006; 231(5): 534 - 544.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
E. Poon, F. Clermont, M. T. Firpo, and R. J. Akhurst
TGF{beta} inhibition of yolk-sac-like differentiation of human embryonic stem-cell-derived embryoid bodies illustrates differences between early mouse and human development
J. Cell Sci., February 15, 2006; 119(4): 759 - 768.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J.-Y. Rho, K. Yu, J.-S. Han, J.-I. Chae, D.-B. Koo, H.-S. Yoon, S.-Y. Moon, K.-K. Lee, and Y.-M. Han
Transcriptional profiling of the developmentally important signalling pathways in human embryonic stem cells
Hum. Reprod., February 1, 2006; 21(2): 405 - 412.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
C. Chen, S. M. Ware, A. Sato, D. E. Houston-Hawkins, R. Habas, M. M. Matzuk, M. M. Shen, and C. W. Brown
The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
Development, January 15, 2006; 133(2): 319 - 329.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
L. Vallier, M. Alexander, and R. A. Pedersen
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells
J. Cell Sci., October 1, 2005; 118(19): 4495 - 4509.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005