| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
EMBRYONIC STEM CELLS: CHARACTERIZATION SERIES |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Key Words. Embryonic stem cell totipotency
Correspondence: Saul J. Sharkis, Ph.D., Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Room 551, 1550 Orleans Street, Baltimore, Maryland 21231, USA. Telephone: 410-955-8508; Fax: 410-502-5742; e-mail: ssharkis{at}jhmi.edu
Received July 5, 2005;
accepted for publication January 26, 2006.
Human embryonic stem cells (hESCs) self-renew indefinitely while maintaining pluripotency. The molecular mechanism underlying hESCs self-renewal and pluripotency is poorly understood. To identify the signaling pathway molecules that maintain the proliferation of hESCs, we performed a microarray analysis comparing an aneuploid H1 hESC line (named H1T) versus euploid H1 hESC line because the H1T hESC line demonstrates a self-renewal advantage while maintaining pluripotency. We find differential gene expression for the Nodal/Activin, fibroblast growth factor (FGF), Wnt, and Hedgehog (Hh) signaling pathways in the H1T line, which implicates each of these molecules in maintaining the undifferentiated state, whereas the bone morphogenic protein (BMP) and Notch pathways could promote hESCs differentiation. Experimentally, we find that Activin A is necessary and sufficient for the maintenance of self-renewal and pluripotency of hESCs and supports long-term feeder and serum-free growth of hESCs. We show that Activin A induces the expression of Oct4, Nanog, Nodal, Wnt3, basic FGF, and FGF8 and suppresses the BMP signal. Our data indicates Activin A as a key regulator in maintenance of the stemness in hESCs. This finding will help elucidate the complex signaling network that maintains the hESC phenotype and function.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 J. Yu and J. A. Thomson Pluripotent stem cell lines Genes & Dev., August 1, 2008; 22(15): 1987 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saha, L. Ji, J. J. de Pablo, and S. P. Palecek TGF{beta}/Activin/Nodal Pathway in Inhibition of Human Embryonic Stem Cell Differentiation by Mechanical Strain Biophys. J., May 15, 2008; 94(10): 4123 - 4133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mayshar, E. Rom, I. Chumakov, A. Kronman, A. Yayon, and N. Benvenisty Fibroblast Growth Factor 4 and Its Novel Splice Isoform Have Opposing Effects on the Maintenance of Human Embryonic Stem Cell Self-Renewal Stem Cells, March 1, 2008; 26(3): 767 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Robson, D. J. Phillips, T. McAlpine, A. Shin, S. Svobodova, T. Toy, V. Pillay, N. Kirkpatrick, D. Zanker, K. Wilson, et al. Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production Blood, March 1, 2008; 111(5): 2733 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Naujokat and T. Saric Concise Review: Role and Function of the Ubiquitin-Proteasome System in Mammalian Stem and Progenitor Cells Stem Cells, October 1, 2007; 25(10): 2408 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Puceat TGF{beta} in the differentiation of embryonic stem cells Cardiovasc Res, May 1, 2007; 74(2): 256 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Agrawal, W.-K. Hofmann, N. Tidow, M. Ehrich, D. v. d. Boom, S. Koschmieder, W. E. Berdel, H. Serve, and C. Muller-Tidow The C/EBP{delta} tumor suppressor is silenced by hypermethylation in acute myeloid leukemia Blood, May 1, 2007; 109(9): 3895 - 3905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
H. Qin, T. Yu, T. Qing, Y. Liu, Y. Zhao, J. Cai, J. Li, Z. Song, X. Qu, P. Zhou, et al. Regulation of Apoptosis and Differentiation by p53 in Human Embryonic Stem Cells J. Biol. Chem., February 23, 2007; 282(8): 5842 - 5852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B Lee, V. Khivansara, M. M Santos, P. Lamba, T. Yuen, S. C Sealfon, and D. J Bernard Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone {beta} subunit transcription J. Mol. Endocrinol., February 1, 2007; 38(2): 315 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Greber, H. Lehrach, and J. Adjaye Fibroblast Growth Factor 2 Modulates Transforming Growth Factor {beta} Signaling in Mouse Embryonic Fibroblasts and Human ESCs (hESCs) to Support hESC Self-Renewal Stem Cells, February 1, 2007; 25(2): 455 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Rao One Successful Series Begets Another Stem Cells, October 1, 2006; 24(10): 2160 - 2161. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| STEM CELLS | THE ONCOLOGIST | CME | ALPHAMED PRESS JOURNALS |
