Investigating monogenic and complex diseases with pluripotent stem cells

Nat Rev Genet. 2011 Apr;12(4):266-75. doi: 10.1038/nrg2951. Epub 2011 Mar 9.


Human genetic studies have revealed the molecular basis of countless monogenic diseases but have been less successful in associating phenotype to genotype in complex multigenic conditions. Pluripotent stem cells (PSCs), which can differentiate into any cell type, offer promise for defining the functional effects of genetic variation. Here, we recount the advantages and practical limitations of coupling PSCs to genome-wide analyses to probe complex genetics and discuss the ability to investigate epigenetic contributions to disease states. We also describe new ways of using mice and mouse embryonic stem cells (ESCs) in tandem with human stem cells to further define genotype-phenotype relationships.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation*
  • Disease / genetics*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Epigenomics
  • Genome
  • Genotype
  • Humans
  • Mice
  • Phenotype
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism