Strand-seq: A unifying tool for studies of chromosome segregation

• Published in: Seminars in cell & developmental biology Vol. 24; no. 8-9; pp. 643 - 652
• Main Authors: Falconer, Ester, Lansdorp, Peter M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2013
• Subjects: Animals; Asymmetric; Chromosome Segregation; Crick; DNA - metabolism; High-Throughput Nucleotide Sequencing - methods; Humans; In Situ Hybridization, Fluorescence; Models, Biological; Non-random; Sister Chromatid Exchange; Strand-seq; Template; Watson; Asymmetric; Strand-seq; Non-random; Watson; Crick; Template
• ISSN: 1084-9521; 1096-3634
• DOI: 10.1016/j.semcdb.2013.04.005

•Non-random segregation proposed as mechanism for genome protection or cell fate specification.•Chromosome segregation studies are limited by reliance on imaging and inferring template strands.•A new method (Strand-seq) can identify all template strands in single cells independently.•We model experiments using Strand-seq to test both Immortal Strand and Silent Sister Hypotheses. Non random segregation of sister chromatids has been implicated to help specify daughter cell fate (the Silent Sister Hypothesis [1]) or to protect the genome of long-lived stem cells (the Immortal Strand Hypothesis [2]). The idea that sister chromatids are non-randomly segregated into specific daughter cells is only marginally supported by data in sporadic and often contradictory studies. As a result, the field has moved forward rather slowly. The advent of being able to directly label and differentiate sister chromatids in vivo using fluorescence in situ hybridization [3] was a significant advance for such studies. However, this approach is limited by the need for large tracks of unidirectional repeats on chromosomes and the reliance on quantitative imaging of fluorescent probes and rigorous statistical analysis to discern between the two competing hypotheses. A novel method called Strand-seq which uses next-generation sequencing to assay sister chromatid inheritance patterns independently for each chromosome [4] offers a comprehensive approach to test for non-random segregation. In addition Strand-seq enables studies on the deposition of chromatin marks in relation to DNA replication. This method is expected to help unify the field by testing previous claims of non-random segregation in an unbiased way in many model systems in vitro and in vivo.