Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133570
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | A molecular roadmap of reprogramming somatic cells into iPS cells |
Author: | Polo, J.M. Anderssen, E. Walsh, R.M. Schwarz, B.A. Nefzger, C.M. Lim, S.M. Borkent, M. Apostolou, E. Alaei, S. Cloutier, J. Bar-Nur, O. Cheloufi, S. Stadtfeld, M. Figueroa, M.E. Robinton, D. Natesan, S. Melnick, A. Zhu, J. Ramaswamy, S. Hochedlinger, K. |
Citation: | Cell, 2012; 151(7):1617-1632 |
Publisher: | Cell Press |
Issue Date: | 2012 |
ISSN: | 0092-8674 1097-4172 |
Statement of Responsibility: | Jose M.Polo, Endre Anderssen, Ryan M.Walsh, Benjamin A.Schwarz, Christian M.Nefzger, Sue Me iLim |
Abstract: | Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is inefficient, complicating mechanistic studies. Here, we examined defined intermediate cell populations poised to becoming iPSCs by genome-wide analyses. We show that induced pluripotency elicits two transcriptional waves, which are driven by c-Myc/Klf4 (first wave) and Oct4/Sox2/Klf4 (second wave). Cells that become refractory to reprogramming activate the first but fail to initiate the second transcriptional wave and can be rescued by elevated expression of all four factors. The establishment of bivalent domains occurs gradually after the first wave, whereas changes in DNA methylation take place after the second wave when cells acquire stable pluripotency. This integrative analysis allowed us to identify genes that act as roadblocks during reprogramming and surface markers that further enrich for cells prone to forming iPSCs. Collectively, our data offer new mechanistic insights into the nature and sequence of molecular events inherent to cellular reprogramming. |
Keywords: | Animals Humans Mice Transcription Factors Cytological Techniques Genome-Wide Association Study Induced Pluripotent Stem Cells Cellular Reprogramming |
Rights: | © 2012 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.cell.2012.11.039 |
Published version: | http://dx.doi.org/10.1016/j.cell.2012.11.039 |
Appears in Collections: | Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.