한빛사논문
- 조회443
Yeongjun Jang1,†, Liana Fasching2,†, Taejeong Bae1, Livia Tomasini2, Jeremy Schreiner2, Anna Szekely3, Thomas V. Fernandez2,4, James F. Leckman2, Flora M. Vaccarino2,5,6,* and Alexej Abyzov1,*
1Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA,
2Child Study Center, Yale University, New Haven, CT 06520, USA,
3Department of Neurology, Yale University, New Haven, CT 06520, USA,
4Department of Psychiatry, Yale University, New Haven, CT 06511, USA,
5Department of Neuroscience, Yale University, New Haven, CT 06520, USA
6Yale Kavli Institute for Neuroscience, New Haven, CT 06520, USA.
*To whom correspondence should be addressed.: Alexej Abyzov
Correspondence may also be addressed to Flora M. Vaccarino.
†The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
Abstract
Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression and during development, starting from the first cell divisions of the zygote. However, this approach requires sampling and analyzing the genomes of multiple cells, which can be redundant in lineage representation, limiting the scalability of the approach. We describe a strategy for cost- and time-efficient lineage reconstruction using clonal induced pluripotent stem cell lines from human skin fibroblasts. The approach leverages shallow sequencing coverage to assess the clonality of the lines, clusters redundant lines and sums their coverage to accurately discover mutations in the corresponding lineages. Only a fraction of lines needs to be sequenced to high coverage. We demonstrate the effectiveness of this approach for reconstructing lineage trees during development and in hematologic malignancies. We discuss and propose an optimal experimental design for reconstructing lineage trees.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-24)
- 국외 연구진
- 생명과학 > 유전학
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