Genetic Engineering & Biotechnology News

JUN15 2018

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GENengnews.com | Genetic Engineering & Biotechnology News | JUNE 15, 2018 | 17 lions of pipetting steps in a fully automated fashion, and it has been used to understand neural stem cell development. "We need to keep cells alive for dynamic high-throughput multiplexed measurements in a spatially resolved manner—ideally, in in- tact tissue to maintain the tissue microenvi- ronment and context," Dr. Tay commented. "Right now, the field is trying to inch for- ward with different approaches, but this is the nirvana of single-cell analysis and would be a quantum leap." Epimutation Rates As cells divide and propagate, they ac- quire errors in their genetic information as well as their epigenetic information, a phe- nomenon termed epimutation. Earlier stud- ies indicated that the average epimutation rate in cancer is significantly elevated as compared to normal tissue. Additional studies are being conducted at the laboratory of Dan Landau, M.D., Ph.D., assistant professor of medicine at Weill Cor- nell Medicine and an associate core member of the New York Genome Center. Dr. Lan- dau and colleagues are using high-through- put multimodality single-cell protocols and integrative analytics to capture the DNA methylome, the transcriptome, and the geno- type of normal and malignant B cells. Multimodality technologies were applied to patient samples with chronic lymphocytic leukemia along with normal B-cell samples to probe the average epimutation rate and the rate distribution within cells. The distribution in normal tissue was quite wide. In contrast, in leukemia samples the distribution was nar- row with uniformly elevated rates. This ob- servation corresponds to epimutation as a molecular clock. Whereas leukemia cells come from a single clonal origin and therefore have a uni- formly high number of divisions, normal B cells have different evolutionary histories; some have just emerged from the bone mar- row, and others are older, reflected by a low or high epimutation rate, respectively. "The epimutation information can also be used as a native lineage tracing system, [allowing investigators] to infer the phy- logenetic relationships between individual cells," explained Dr. Landau. "With this approach, high-resolution lineage trees are created directly from primary patient can- cer samples." The topography features of the malig- nant lineage trees are consistent with clonal transformation, demonstrating strong drift early after transformation, and long branch lengths, a result of the high division rate in cancer. In contrast, normal B-cell lineages show deeper structures due to the differ- entiation of one cell type to another, with shorter branch lengths commensurate with lower numbers of divisions in their histories. Since the methylome, transcriptome, and genotype of the single cells are captured, ge- notypic and transcriptional information can be projected on to the lineage tree, allowing clonal divergence to be defined as well as heritable transcriptional variation. This ap- proach was also applied to study the evo- lutionary dynamics that occur as patients receive therapy. Even in genetically homogeneous popu- lations, cells with shared lineage histories could be identified that were differentially impacted by with therapy. The joint tran- scriptional information further allowed the study of the potential mechanism for the differential response to therapy among cells Accurate quality assessment of extracted genomic DNA from biobank samples is important prior to long-term storage and critical for some downstream applications. The FEMTO Pulse from AATI measures the size and concentration of extracted genomic DNA, helping you identify the appropriate high molecular weight DNA samples suitable for optical mapping or long-read sequencing. R aati-us.com BRING BIOBANK SAMPLES INTO FOCUS See how the FEMTO Pulse can improve your downstream application outcomes when using biobank samples. See Single-Cell Analysis on page 18 OMICS Mosaic-Seq was developed to systematically perturb enhancers and measure their endogenous activities at single-cell resolution. This high-throughput technique uses a CRISPR barcoding system to jointly measure a cell's transcriptome and its sgRNA modulators, thus quantifying the effects of dCas9-KRAB-mediated enhancer repression in single cells.

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