4.8 Article

A predictive computational framework for direct reprogramming between human cell types

期刊

NATURE GENETICS
卷 48, 期 3, 页码 331-335

出版社

NATURE PORTFOLIO
DOI: 10.1038/ng.3487

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资金

  1. Biotechnology and Biological Sciences research council
  2. Japanese Society for the Promotion of Science
  3. Silvia and Charles Senior Medical Viertel Fellowship
  4. Metcalf award from the National Stem Cell Foundation of Australia
  5. National Health and Medical Research Council of Australia (NHMRC) project [APP1085302]
  6. Australia Research Council's special initiative Stem Cells Australia
  7. RIKEN Omics Science Center from MEXT
  8. Innovative Technology (Cell Innovation Program) from MEXT, Japan
  9. Biotechnology and Biological Sciences research council
  10. Japanese Society for the Promotion of Science
  11. Silvia and Charles Senior Medical Viertel Fellowship
  12. Metcalf award from the National Stem Cell Foundation of Australia
  13. National Health and Medical Research Council of Australia (NHMRC) project [APP1085302]
  14. Australia Research Council's special initiative Stem Cells Australia
  15. RIKEN Omics Science Center from MEXT
  16. Innovative Technology (Cell Innovation Program) from MEXT, Japan
  17. Biotechnology and Biological Sciences Research Council [BB/I025018/1] Funding Source: researchfish
  18. Medical Research Council [MC_U120097112] Funding Source: researchfish
  19. BBSRC [BB/I025018/1] Funding Source: UKRI
  20. MRC [MC_U120097112] Funding Source: UKRI

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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.

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