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Dissecting single-cell genomes through the clonal organoid technique

  • 작성자

    Young Seok Ju
  • 작성일자

    2021-11-29
  • 조회수

    5
Young Seok Ju( ysju@kaist.ac.kr )
2015-present PI, KAIST, Graduate School of Medical Science and Engineering
2013-2015 Postdoc, Cancer Genome Project, Wellcome Sanger Institute
2007-2010 Phd, Dept of Biochemistry, Seoul National Univ. College of Medicine
2001-2007 MD, Seoul National Univ. College of Medicine

Dissecting single-cell genomes through the clonal organoid technique

The revolution in genome sequencing technologies has enabled the comprehensive detection of genomic variations in human cells, including inherited germline polymorphisms, de novo mutations, and postzygotic mutations. When these technologies are combined with techniques for isolating and expanding single-cell DNA, the landscape of somatic mosaicism in an individual body can be systematically revealed at a single-cell resolution. Here, we summarize three strategies (whole-genome amplification, microdissection of clonal patches in the tissue, and in vitro clonal expansion of single cells) that are currently applied for single-cell mutational analyses. Among these approaches, in vitro clonal expansion, particularly via adult stem cell-derived organoid culture technologies, yields the most sensitive and precise catalog of somatic mutations in single cells. Moreover, because it produces living mutant cells, downstream validation experiments and multiomics profiling are possible. Through the synergistic combination of organoid culture and genome sequencing, researchers can track genome changes at a single-cell resolution, which will lead to new discoveries that were previously impossible.

Exp Mol Med. 2021 Oct;53(10):1503-1511. doi: 10.1038/s12276-021-00680-1. Epub 2021 Oct 18.
https://pubmed.ncbi.nlm.nih.gov/34663940/