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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 12 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 2, pages 282–292, February 2013
How to Cite
Park, K.-S., Cha, Y., Kim, C.-H., Ahn, H.-J., Kim, D., Ko, S., Kim, K.-H., Chang, M.-Y., Ko, J.-H., Noh, Y.-S., Han, Y.-M., Kim, J., Song, J., Kim, J. Y., Tesar, P. J., Lanza, R., Lee, K.-A. and Kim, K.-S. (2013), Transcription Elongation Factor Tcea3 Regulates the Pluripotent Differentiation Potential of Mouse Embryonic Stem Cells Via the Lefty1-Nodal-Smad2 Pathway. STEM CELLS, 31: 282–292. doi: 10.1002/stem.1284
Author contributions: K.-S.P. and K.-S.K.: concept and design, data analysis and interpretation, and writing; Y.C.: concept and design, collection and/or assembly of data, and data analysis and interpretation; C.-H.K., H.-J.A., D.K., S.K., K.-H.K., M.-Y.C., J.-H.K., J.Y.K., J.K., and J.S.: collection and/or assembly of data; Y.-S.N., Y.-M.H., P.J.T., R.L., and K.-A.L.: data analysis and interpretation. K.-S.P. and Y.C. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 25, 2012.
- Issue published online: 12 FEB 2013
- Article first published online: 12 FEB 2013
- Accepted manuscript online: 21 NOV 2012 12:33AM EST
- Manuscript Accepted: 25 OCT 2012
- Manuscript Received: 6 JUL 2012
- Korea Science and Engineering Foundation (KOSEF)
- Korean government (MEST). Grant Numbers: 2012-050367, 2012-0005261
- Priority Research Centers Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science, and Technology. Grant Number: 2012-0006679
- National Institute of Health (NIH). Grant Numbers: MH087903, HL106627, NS070577
- Mouse embryonic stem cells
Self-renewal and pluripotency are hallmark properties of pluripotent stem cells, including embryonic stem cells (ESCs) and iPS cells. Previous studies revealed the ESC-specific core transcription circuitry and showed that these core factors (e.g., Oct3/4, Sox2, and Nanog) regulate not only self-renewal but also pluripotent differentiation. However, it remains elusive how these two cell states are regulated and balanced during in vitro replication and differentiation. Here, we report that the transcription elongation factor Tcea3 is highly enriched in mouse ESCs (mESCs) and plays important roles in regulating the differentiation. Strikingly, altering Tcea3 expression in mESCs did not affect self-renewal under nondifferentiating condition; however, upon exposure to differentiating cues, its overexpression impaired in vitro differentiation capacity, and its knockdown biased differentiation toward mesodermal and endodermal fates. Furthermore, we identified Lefty1 as a downstream target of Tcea3 and showed that the Tcea3-Lefty1-Nodal-Smad2 pathway is an innate program critically regulating cell fate choices between self-replication and differentiation commitment. Together, we propose that Tcea3 critically regulates pluripotent differentiation of mESCs as a molecular rheostat of Nodal-Smad2/3 signaling. STEM CELLS2013;31:282–292