To facilitate understanding the mechanisms of somatic reprogramming to human induced Pluripotent Stem Cells (iPSCs), we have established intermediately Reprogrammed Stem Cells (iRSCs), human mesenchymal cells that express exogenous Oct4/Sox2/Klf4/c-Myc (OSKM) and endogenous SOX2/NANOG. iRSCs can be stably maintained at low density. At high density, however, they are induced to enter Mesenchymal-to-Epithelial Transition (MET), resulting in reprogramming to an iPSC state. Morphological changes through MET correlate with silencing of exogenous OSKM, and up-regulation of endogenous OCT4. A CRISPR/Cas9-mediated GFP knock-in visualized the temporal regulation of endogenous OCT4 in cells converting from iRSC to iPSC state. OCT4 activation coincident with OSKM silencing occurred prior to entering MET. Notably, OCT4 instability was frequently observed in cells of developing post-MET colonies until a late stage (>200 cells), demonstrating that OCT4-activated post-MET cells switched from asymmetric to symmetric cell division in late stage reprogramming.
OCT4 Activity during Conversion of Human Intermediately Reprogrammed Stem Cells to iPS Cells through MET
Currently Viewing Accepted Manuscript - Newer Version Available
Rika Teshigawara, Kunio Hirano, Shogo Nagata, Justin Ainscough, Takashi Tada; OCT4 Activity during Conversion of Human Intermediately Reprogrammed Stem Cells to iPS Cells through MET. Development 2015; dev.130344. doi: https://doi.org/10.1242/dev.130344
Download citation file:
Advertisement
Call for papers: Uncovering Developmental Diversity
Development invites you to submit your latest research to our upcoming special issue: Uncovering Developmental Diversity. This issue will be coordinated by our academic Editor Cassandra Extavour (Harvard University, USA) alongside two Guest Editors: Liam Dolan (Gregor Mendel Institute of Molecular Plant Biology, Austria) and Karen Sears (University of California Los Angeles, USA).
Choose Development in 2024
In this Editorial, Development Editor-in-Chief James Briscoe and Executive Editor Katherine Brown explain how you support your community by publishing in Development and how the journal champions serious science, community connections and progressive publishing.
Journal Meeting: From Stem Cells to Human Development
Register now for the 2024 Development Journal Meeting From Stem Cells to Human Development. Early-bird registration deadline: 3 May. Abstract submission deadline: 21 June.
Pluripotency of a founding field: rebranding developmental biology
This collaborative Perspective, the result of a workshop held in 2023, proposes a set of community actions to increase the visibility of the developmental biology field. The authors make recommendations for new funding streams, frameworks for collaborations and mechanisms by which members of the community can promote themselves and their research.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.