Dataset Information

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

ABSTRACT: Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging of cell shape, proliferation, and other phenotypes with gene expression and DNA sequence datasets from over 100 human iPSC lines. By applying a dimensionality reduction approach, Probabilistic Estimation of Expression Residuals (PEER), we extracted factors that captured the effects of intrinsic (genetic concordance between different cell lines from the same donor) and extrinsic (cell responses to different fibronectin concentrations) conditions. We identify genes that correlate in expression with intrinsic and extrinsic PEER factors and associate outlier cell behavior with genes containing rare deleterious non-synonymous SNVs. Our study, thus, establishes a strategy for examining the genetic basis of inter-individual variability in cell behavior.

SUBMITTER: Vigilante A

PROVIDER: S-EPMC6381787 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

Vigilante Alessandra A Laddach Anna A Moens Nathalie N Meleckyte Ruta R Leha Andreas A Ghahramani Arsham A Culley Oliver J OJ Kathuria Annie A Hurling Chloe C Vickers Alice A Wiseman Erika E Tewary Mukul M Zandstra Peter W PW Durbin Richard R Fraternali Franca F Stegle Oliver O Birney Ewan E Luscombe Nicholas M NM Danovi Davide D Watt Fiona M FM

Cell reports 20190201 8

Large cohorts of human induced pluripotent stem cells (iPSCs) from healthy donors are a potentially powerful tool for investigating the relationship between genetic variants and cellular behavior. Here, we integrate high content imaging of cell shape, proliferation, and other phenotypes with gene expression and DNA sequence datasets from over 100 human iPSC lines. By applying a dimensionality reduction approach, Probabilistic Estimation of Expression Residuals (PEER), we extracted factors that c ...[more]

PMID: 30784590

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Project description:Yellow-bellied toad populations (Bombina variegata) show a wide fast-slow continuum of the life-history trait longevity ranging from 5 to 23 years. We investigated populations in Germany (n = 8) and Austria (n = 1) to determine their position within the continuum of longevity and the potential drivers of adult survival at the local and the continental scale. Intrinsic and extrinsic factors considered were local weather, nutritional state, allocation of ingested energy to somatic growth, pathogen prevalence, and geographical clines (latitude, altitude, and longitude). Capture-mark-recapture (CMR) monitoring and direct age assessment by skeletochronology allowed for reliable estimates of longevity and adult survival. Raw and corrected recapture rates as well as a probabilistic estimate of the lifespan of the eldest 1% adults of a cohort (CMR data) were used as surrogates for adult survival and thus longevity in a population. Additionally, survival rates were calculated from static life tables based on the age structure (skeletochronological data) of eight populations. Populations in Germany were short-lived with a maximum lifespan of annual cohorts varying from 5 to 8 years, whereas the population in Austria was long-lived with a cohort longevity of 13 to 23 years. We provide evidence that annual survival rates and longevity differ among years and between short- and long-lived populations, but there was no decrease of survival in older toads (i.e. absence of senescence). Variation of weather among years accounted for 90.7% of variance in annual survival rates of short-lived populations, whereas the sources of variation in the long-lived population remained unidentified. At the continental scale, longevity variation among B. variegata populations studied so far did not correspond to geographical clines or climate variation. Therefore, we propose that a population's position within the fast-slow continuum integrates the response to local environmental stochasticity (extrinsic source of variation) and the efficiency of chemical antipredator protection determining the magnitude of longevity (intrinsic source of variation).

Dataset Information

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

Publications

Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.

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