| Literature DB >> 28976365 |
Sai Teja Pusuluri1, Alex H Lang2, Pankaj Mehta2, Horacio Castillo3.
Abstract
Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an open problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple one-dimensional reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges from epigenetic landscape models where cellular reprogramming is viewed as a "barrier-crossing" process between cell fates. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an "optimal path" in gene expression space for reprogramming.Keywords: cell reprogramming; direct conversion; epigenetic landscape; reprogramming dynamics; spin glass physics
Year: 2017 PMID: 28976365 PMCID: PMC6482097 DOI: 10.1088/1478-3975/aa90e0
Source DB: PubMed Journal: Phys Biol ISSN: 1478-3967 Impact factor: 2.583