In situ sequencing for RNA analysis in preserved tissue and cells

Nat Methods. 2013 Sep;10(9):857-60. doi: 10.1038/nmeth.2563. Epub 2013 Jul 14.


Tissue gene expression profiling is performed on homogenates or on populations of isolated single cells to resolve molecular states of different cell types. In both approaches, histological context is lost. We have developed an in situ sequencing method for parallel targeted analysis of short RNA fragments in morphologically preserved cells and tissue. We demonstrate in situ sequencing of point mutations and multiplexed gene expression profiling in human breast cancer tissue sections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Point Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptor, ErbB-2 / genetics
  • Sequence Analysis, RNA / methods*
  • Tissue Preservation / methods*
  • ras Proteins / genetics


  • Actins
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins