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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 20 SEP 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 10, pages 2199–2211, October 2012
How to Cite
Wang, C.-H., Ma, N., Lin, Y.-T., Wu, C.-C., Hsiao, M., Lu, F. L., Yu, C.-C., Chen, S.-Y. and Lu, J. (2012), A shRNA Functional Screen Reveals Nme6 and Nme7 Are Crucial for Embryonic Stem Cell Renewal. STEM CELLS, 30: 2199–2211. doi: 10.1002/stem.1203
Author contribution: C.H.W.: collection and assemble the data, data analysis and interpretation, manuscript writing, and final approval of the manuscript; N.M., L.F.L., and S.Y.C.: manuscript writing and final approval of the manuscript; Y.T.L.: collection and assemble the data, data analysis and interpretation, and final approval of the manuscript; C.C.W.: collection and assemble the data and final approval of the manuscript; M.H.: provision study material and final approval of the manuscript; C.C.Y.: collection and assemble the data and data analysis and interpretation; J.L.: data analysis and interpretation, manuscript writing, and final approval of the manuscript. C.-H.W., N.M., and Y.-T. Lin 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 August 16, 2012.
- Issue published online: 20 SEP 2012
- Article first published online: 20 SEP 2012
- Accepted manuscript online: 16 AUG 2012 03:18PM EST
- Manuscript Accepted: 3 JUL 2012
- Manuscript Received: 14 DEC 2011
- National Health Research Institutes. Grant Number: NHRI-EX100-10025SI
- National Science Council. Grant Numbers: NSC-100-2314-B-001-002 NSC-97-2321-B-001-022-MY3, NSC-100-2321-B-001-039-
- National RNAi Core facility
- National Research Program for Biopharmaceuticals (NRPB)
- Embryonic stem cells;
- Embryoid body;
In contrast to the somatic cells, embryonic stem cells (ESCs) are characterized by its immortalization ability, pluripotency, and oncogenicity. Revealing the underlying mechanism of ESC characteristics is important for the application of ESCs in clinical medicine. We performed systematic functional screen in mouse ESCs with 4,801 shRNAs that target 929 kinases and phosphatases. One hundred and thirty-two candidate genes that regulate both ESC expansion and stem cell marker expression were identified. Twenty-seven out of the 132 genes were regarded as most important since knockdown of each gene induces morphological changes from undifferentiated to differentiated state. Among the 27 genes, we chose nonmetastatic cell 6 (Nme6, also named as Nm23-H6) and nonmetastatic cell 7 (Nme7, also designated as Nm23-H7) to study first. Nme6 and Nme7 both belong to the members of nucleoside diphosphate kinase family. We demonstrate that Nme6 and Nme7 are important for the regulation of Oct4, Nanog, Klf4, c-Myc, telomerase, Dnmt3B, Sox2, and ERas expression. Either knockdown of Nme6 or Nme7 reduces the formation of embryoid body (EB) and teratoma. The overexpression of either Nme6 or Nme7 can rescue the stem cell marker expression and the EB formation in the absence of leukemia inhibiting factor. This implies the importance of Nme6 and Nme7 in ESC renewal. This finding not only pinpoints Nme6 or Nme7 can regulate several critical regulators in ESC renewal but also increases our understanding of the ESC renewal and oncogenesis. STEM Cells2012;30:2199–2211