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A reversible haploid mouse embryonic stem cell biobank resource for functional genomics

Elling, U; Wimmer, RA; Leibbrandt, A; Urkard, TB; Michlits, G; Leopoldi, A; Micheler, T; ... Penninger, JM; + view all (2017) A reversible haploid mouse embryonic stem cell biobank resource for functional genomics. Nature , 550 pp. 114-118. 10.1038/nature24027. Green open access

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Abstract

The ability to directly uncover the contributions of genes to a given phenotype is fundamental for biology research. However, ostensibly homogeneous cell populations exhibit large clonal variance1,2 that can confound analyses and undermine reproducibility3. Here we used genome-saturated mutagenesis to create a biobank of over 100,000 individual haploid mouse embryonic stem (mES) cell lines targeting 16,970 genes with genetically barcoded, conditional and reversible mutations. This Haplobank is, to our knowledge, the largest resource of hemi/homozygous mutant mES cells to date and is available to all researchers. Reversible mutagenesis overcomes clonal variance by permitting functional annotation of the genome directly in sister cells. We use the Haplobank in reverse genetic screens to investigate the temporal resolution of essential genes in mES cells, and to identify novel genes that control sprouting angiogenesis and lineage specification of blood vessels. Furthermore, a genome-wide forward screen with Haplobank identified PLA2G16 as a host factor that is required for cytotoxicity by rhinoviruses, which cause the common cold. Therefore, clones from the Haplobank combined with the use of reversible technologies enable high-throughput, reproducible, functional annotation of the genome.

Type: Article
Title: A reversible haploid mouse embryonic stem cell biobank resource for functional genomics
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nature24027
Publisher version: http://dx.doi.org/10.1038/nature24027
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Density-Lipoprotein Receptor, Preimplantation Development, Mammalian-Cells, Essential Genes, Rnai Screens, Angiogenesis, Identification, Heterogeneity, Mutagenesis, Transposon
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/10046774
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