Retrospective cell lineage reconstruction in humans by using short tandem repeats

Liming Tao, Ofir Raz, Zipora Marx, Manjusha S. Ghosh, Sandra Huber, Julia Greindl-Junghans, Tamir Biezuner, Shiran Amir, Lilach Milo, Rivka Adar, Ron Levy, Amos Onn, Noa Chapal-Ilani, Veronika Berman, Asaf Ben Arie, Guy Rom, Barak Oron, Ruth Halaban, Zbigniew T. Czyz, Melanie Werner-KleinChristoph A. Klein, Ehud Shapiro

Research output: Contribution to journalArticlepeer-review


Cell lineage analysis aims to uncover the developmental history of an organism back to its cell of origin. Recently, novel in vivo methods utilizing genome editing enabled important insights into the cell lineages of animals. In contrast, human cell lineage remains restricted to retrospective approaches, which still lack resolution and cost-efficient solutions. Here, we demonstrate a scalable platform based on short tandem repeats targeted by duplex molecular inversion probes. With this human cell lineage tracing method, we accurately reproduced a known lineage of DU145 cells and reconstructed lineages of healthy and metastatic single cells from a melanoma patient who matched the anatomical reference while adding further refinements. This platform allowed us to faithfully recapitulate lineages of developmental tissue formation in healthy cells. In summary, our lineage discovery platform can profile informative somatic mutations efficiently and provides solid lineage reconstructions even in challenging low-mutation-rate healthy single cells.

Original languageEnglish
Article number100054
JournalCell Reports Methods
Issue number3
StatePublished - 26 Jul 2021
Externally publishedYes


  • cell lineage reconstruction
  • molecular inversion probes
  • short tandem repeats
  • single-cell genomics


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