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Embryonic Stem Cells/induced Pluripotent Stem Cells
Article first published online: 24 APR 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 5, pages 918–927, May 2013
How to Cite
Chang, K.-H. and Li, M. (2013), Clonal Isolation of an Intermediate Pluripotent Stem Cell State. STEM CELLS, 31: 918–927. doi: 10.1002/stem.1330
Author contributions: K.H.C.: concept and design, execution of all experiments, data analysis and interpretation, obtained funding, and wrote the paper; M.L.: concept and design, data analysis and interpretation, obtained funding, and wrote and finalized the paper.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS January 22, 2013.
- Issue published online: 24 APR 2013
- Article first published online: 24 APR 2013
- Accepted manuscript online: 22 JAN 2013 08:53AM EST
- Manuscript Accepted: 13 DEC 2012
- Manuscript Received: 30 JUL 2012
- Chang Gung Memorial Hospital, Taipei, Taiwan. Grant Number: CMRPG 360041-43 and 3A0691-93
- UK Medical Research Council. Grant Number: G117/560 and U120005004
- National Science Council, Executive Yuan, Taiwan. Grant Number: NSC 100-2314-B-182A-076-MY1-2
- Embryonic stem cells;
- Epiblast stem cells
Pluripotent stem cells of different embryonic origin respond to distinct signaling pathways. Embryonic stem cells (ESCs), which are derived from the inner cell mass of preimplantation embryos, are dependent on LIF-Stat3 signaling, while epiblast stem cells (EpiSCs), which are established from postimplantation embryos, require activin-Smad2/3 signaling. Recent studies have revealed heterogeneity of ESCs and the presence of intermediate pluripotent stem cell populations, whose responsiveness to growth factors, gene expression patterns, and associated chromatic signatures are compatible to a state in between ESCs and EpiSCs. However, it remains unknown whether such cell populations represent a stable entity at single-cell level. Here, we describe the identification of clonal stem cells from mouse ESCs with global gene expression profiles representing such a state. These pluripotent stem cells display dual responsiveness to LIF-Stat3 and activin-Smad2/3 at single-cell level and thus named as intermediate epiblast stem cells (IESCs). Furthermore, these cells show accelerated temporal gene expression kinetics during embryoid body differentiation in vitro consistent with a more advanced differentiation stage than that of ESCs. The successful isolation of IESCs supports the notion that traverse from naïve ground state toward lineage commitment occurs gradually in which transition milestones can be captured as clonogenic entity. Our finding provides a new model to better understand the multiple pluripotent states. STEM CELLS 2013;31:918–927