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Nat Genet. 2016 Mar;48(3):331-5. doi: 10.1038/ng.3487. Epub 2016 Jan 18.

A predictive computational framework for direct reprogramming between human cell types.

Author information

1
Department of Computer Science, University of Bristol, Bristol, UK.
2
Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore.
3
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
4
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
5
Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
6
RIKEN Omics Science Center, Yokohama, Japan (ceased to exist as of 1 April 2013 owing to reorganization).
7
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
8
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
9
Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
10
RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Japan.

Abstract

Transdifferentiation, the process of converting from one cell type to another without going through a pluripotent state, has great promise for regenerative medicine. The identification of key transcription factors for reprogramming is currently limited by the cost of exhaustive experimental testing of plausible sets of factors, an approach that is inefficient and unscalable. Here we present a predictive system (Mogrify) that combines gene expression data with regulatory network information to predict the reprogramming factors necessary to induce cell conversion. We have applied Mogrify to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming. Mogrify correctly predicts the transcription factors used in known transdifferentiations. Furthermore, we validated two new transdifferentiations predicted by Mogrify. We provide a practical and efficient mechanism for systematically implementing novel cell conversions, facilitating the generalization of reprogramming of human cells. Predictions are made available to help rapidly further the field of cell conversion.

PMID:
26780608
DOI:
10.1038/ng.3487
[Indexed for MEDLINE]

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