Notch inhibition allows oncogene-independent generation of iPS cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-08

AUTHORS

Justin K Ichida, TCW Julia, Luis A Williams, Ava C Carter, Yingxiao Shi, Marcelo T Moura, Michael Ziller, Sean Singh, Giovanni Amabile, Christoph Bock, Akihiro Umezawa, Lee L Rubin, James E Bradner, Hidenori Akutsu, Alexander Meissner, Kevin Eggan

ABSTRACT

The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially dangerous oncogenes KLF4 and CMYC or the genetic inhibition of the tumor suppressor gene p53. We hypothesized that inhibition of signal transduction pathways that promote differentiation of the target somatic cells during development might relieve the requirement for non-core pluripotency factors during induced pluripotent stem cell (iPSC) reprogramming. Here, we show that inhibition of Notch greatly improves the efficiency of iPSC generation from mouse and human keratinocytes by suppressing p21 in a p53-independent manner and thereby enriching for undifferentiated cells capable of long-term self-renewal. Pharmacological inhibition of Notch enabled routine production of human iPSCs without KLF4 and CMYC while leaving p53 activity intact. Thus, restricting the development of somatic cells by altering intercellular communication enables the production of safer human iPSCs. More... »

PAGES

632

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nchembio.1552

DOI

http://dx.doi.org/10.1038/nchembio.1552

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023910067

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24952596


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