Single-Cell Template Strand Sequencing by Strand-Seq Enables the Characterization of Individual Homologs
This week we profile a recent publication in Nature Protocols from the laboratory of Dr. Peter Lansdorp at the BC Cancer Agency.
What is your lab’s current research focus?
My research is and has been focused on the role of genome instability in stem cells in aging and cancer. My lab has a track-record of developing novel research tools, many of which are still in widespread use e.g. commercialized by STEMCELL Technologies and other biotech companies. These include monoclonal antibodies, an IL-6 dependent cell line, cell separation techniques and methods to measure the length of telomere repeat in chromosomes and cells. Recently, we developed a powerful single cell sequencing technique called Strand-seq. We now want to use this powerful method to explore new frontiers in stem cell biology, DNA repair and human genomic diversity.
What is the significance of the findings in this publication?
The paper describes the Strand-seq method which was developed over the last 5 years by a team of very talented people including Ester Falconer, Mark Hills, Ashley Sanders and Diana Spierings. The paper provides details of our method and some of its applications. The significance of the paper is that it will allow others to use the method and explore novel avenues in their studies.
Briefly, what are the next steps for this research?
Specifically, we next want to explore Strand-seq to answer some basic questions in biology and medicine:
- What are the molecular mechanisms that regulate stem cell self-renewal and differentiation? By combining single-cell Strand-seq with the analysis of transcripts in the same cell, we will study the maintenance of epigenetic information in the context of directional DNA replication in single cells, an aspect of cell biology that has not been subject to experimentation before.
- What are the molecular mechanisms involved in DNA repair? By mapping sister chromatid exchange events, copy number variations, polymorphic inversions and loss of heterozygosity in single cells we have a unique approach to study DNA repair events. Studies with cells before and after specific genetic alterations will allow us to generate new insight into the molecular pathways that are involved in cancer, specific diseases and aging.
- Mapping of polymorphic inversions in completely-phased “personalized genomes” for “precision medicine”. Ongoing studies have revealed that Strand-seq by itself, but especially in combination with other sequencing approaches, yields unprecedented precise information about the genome of an individual.
In summary, we want to use the Strand-seq approach, not only to study the amount of DNA in single cells, but also to examine genomic changes in single cells, individual DNA repair reactions, and importantly, the DNA that we inherited from our parents without having to study their DNA directly. By combining novel genotype information with various phenotypes we are confident to advance knowledge in many different areas.