Dataset Information

Multiplex recording of cellular events over time on CRISPR biological tape.

ABSTRACT: Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a "biological tape recorder" in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.

SUBMITTER: Sheth RU

PROVIDER: S-EPMC7869111 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Multiplex recording of cellular events over time on CRISPR biological tape.

Sheth Ravi U RU Yim Sung Sun SS Wu Felix L FL Wang Harris H HH

Science (New York, N.Y.) 20171123 6369

Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a "biological tape recorder" in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording ov ...[more]

PMID: 29170279

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Project description:Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage. We also investigated if rate of change in BA was associated with changes in depressive symptoms over time. Youths aged 8-16 years at baseline self-reported Tanner stage and depressive symptoms at baseline and follow-up and provided saliva samples for DNA at both assessments. Horvath epigenetic age estimates were derived from DNA methylation data measured with the Illumina EPIC array. At follow-up, contextual threat interviews were administered to youths and caregivers to assess youths' experiences of past-year SLEs. Interviews were objectively coded by an independent rating team to generate a SLE impact score, reflecting the severity of all SLEs occurring over the prior year. Rate of change in BA metrics was operationalized as change in epigenetic age or Tanner stage as a function of time between assessments. Higher objective SLE impact scores over follow-up were related to a greater rate of change in epigenetic age (β = 0.21, p = .043). Additionally, among youths with lower-but not higher-Tanner stage at baseline, there was a positive association of SLE impact scores with rate of change in Tanner stage (Baseline Tanner Stage × SLE Impact Score interaction: β = - 0.21, p = .011). A greater rate of change in epigenetic age was also associated with higher depressive symptom levels at follow-up, adjusting for baseline symptoms (β = 0.15, p = .043). Associations with epigenetic age were similar, although slightly attenuated, when adjusting for epithelial (buccal) cell proportions. Whereas much research in youths has focused on severe experiences of early adversity, we demonstrate that more commonly experienced SLEs during adolescence may also contribute to accelerated BA. Further research is needed to understand the long-term consequences of changes in BA metrics for health.

Dataset Information

Multiplex recording of cellular events over time on CRISPR biological tape.

Publications

Multiplex recording of cellular events over time on CRISPR biological tape.

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