A reversible gene trap collection empowers haploid genetics in human cells

Tilmann Bürckstümmer; Carina Banning; Philipp Hainzl; Richard Schobesberger; Claudia Kerzendorfer; Florian M. Pauler; Doris Chen; Nicole Them; Fiorella Schischlik; Manuele Rebsamen; Michal Smida; Ferran Fece De La Cruz; Ana Lapao; Melissa Liszt; Benjamin Eizinger; Philipp M. Guenzl; Vincent A. Blomen; Tomasz Konopka; Bianca Gapp; Katja Parapatics; Barbara Maier; Johannes Stöckl; Wolfgang Fischl; Sejla Salic; M. Rita Taba Casari; Sylvia Knapp; Keiryn L. Bennett; Christoph Bock; Jacques Colinge; Robert Kralovics; Gustav Ammerer; Georg Casari; Thijn R. Brummelkamp; Giulio Superti-Furga; Sebastian M.B. Nijman

doi:10.1038/nmeth.2609

A reversible gene trap collection empowers haploid genetics in human cells

Tilmann Bürckstümmer, Carina Banning, Philipp Hainzl, Richard Schobesberger, Claudia Kerzendorfer, Florian M. Pauler, Doris Chen, Nicole Them, Fiorella Schischlik, Manuele Rebsamen, Michal Smida, Ferran Fece De La Cruz, Ana Lapao, Melissa Liszt, Benjamin Eizinger, Philipp M. Guenzl, Vincent A. Blomen, Tomasz Konopka, Bianca Gapp, Katja ParapaticsBarbara Maier, Johannes Stöckl, Wolfgang Fischl, Sejla Salic, M. Rita Taba Casari, Sylvia Knapp, Keiryn L. Bennett, Christoph Bock, Jacques Colinge, Robert Kralovics, Gustav Ammerer, Georg Casari, Thijn R. Brummelkamp, Giulio Superti-Furga, Sebastian M.B. Nijman

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Abstract

Knockout collections are invaluable tools for studying model organisms such as yeast. However, there are no large-scale knockout collections of human cells. Using gene-trap mutagenesis in near-haploid human cells, we established a platform to generate and isolate individual 'gene-trapped cells' and used it to prepare a collection of human cell lines carrying single gene-trap insertions. In most cases, the insertion can be reversed. This growing library covers 3,396 genes, one-third of the expressed genome, is DNA-barcoded and allows systematic screens for a wide variety of cellular phenotypes. We examined cellular responses to TNF-α, TGF-β, IFN-γ and TNF-related apoptosis-inducing ligand (TRAIL), to illustrate the value of this unique collection of isogenic human cell lines.

Original language	English
Pages (from-to)	965-971
Number of pages	7
Journal	Nature Methods
Volume	10
Issue number	10
DOIs	https://doi.org/10.1038/nmeth.2609
State	Published - Oct 2013
Externally published	Yes

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Bürckstümmer, T., Banning, C., Hainzl, P., Schobesberger, R., Kerzendorfer, C., Pauler, F. M., Chen, D., Them, N., Schischlik, F., Rebsamen, M., Smida, M., De La Cruz, F. F., Lapao, A., Liszt, M., Eizinger, B., Guenzl, P. M., Blomen, V. A., Konopka, T., Gapp, B., ... Nijman, S. M. B. (2013). A reversible gene trap collection empowers haploid genetics in human cells. Nature Methods, 10(10), 965-971. https://doi.org/10.1038/nmeth.2609

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title = "A reversible gene trap collection empowers haploid genetics in human cells",

abstract = "Knockout collections are invaluable tools for studying model organisms such as yeast. However, there are no large-scale knockout collections of human cells. Using gene-trap mutagenesis in near-haploid human cells, we established a platform to generate and isolate individual 'gene-trapped cells' and used it to prepare a collection of human cell lines carrying single gene-trap insertions. In most cases, the insertion can be reversed. This growing library covers 3,396 genes, one-third of the expressed genome, is DNA-barcoded and allows systematic screens for a wide variety of cellular phenotypes. We examined cellular responses to TNF-α, TGF-β, IFN-γ and TNF-related apoptosis-inducing ligand (TRAIL), to illustrate the value of this unique collection of isogenic human cell lines.",

author = "Tilmann B{\"u}rckst{\"u}mmer and Carina Banning and Philipp Hainzl and Richard Schobesberger and Claudia Kerzendorfer and Pauler, {Florian M.} and Doris Chen and Nicole Them and Fiorella Schischlik and Manuele Rebsamen and Michal Smida and {De La Cruz}, {Ferran Fece} and Ana Lapao and Melissa Liszt and Benjamin Eizinger and Guenzl, {Philipp M.} and Blomen, {Vincent A.} and Tomasz Konopka and Bianca Gapp and Katja Parapatics and Barbara Maier and Johannes St{\"o}ckl and Wolfgang Fischl and Sejla Salic and {Taba Casari}, {M. Rita} and Sylvia Knapp and Bennett, {Keiryn L.} and Christoph Bock and Jacques Colinge and Robert Kralovics and Gustav Ammerer and Georg Casari and Brummelkamp, {Thijn R.} and Giulio Superti-Furga and Nijman, {Sebastian M.B.}",

year = "2013",

month = oct,

doi = "10.1038/nmeth.2609",

language = "English",

volume = "10",

pages = "965--971",

journal = "Nature Methods",

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Bürckstümmer, T, Banning, C, Hainzl, P, Schobesberger, R, Kerzendorfer, C, Pauler, FM, Chen, D, Them, N, Schischlik, F, Rebsamen, M, Smida, M, De La Cruz, FF, Lapao, A, Liszt, M, Eizinger, B, Guenzl, PM, Blomen, VA, Konopka, T, Gapp, B, Parapatics, K, Maier, B, Stöckl, J, Fischl, W, Salic, S, Taba Casari, MR, Knapp, S, Bennett, KL, Bock, C, Colinge, J, Kralovics, R, Ammerer, G, Casari, G, Brummelkamp, TR, Superti-Furga, G & Nijman, SMB 2013, 'A reversible gene trap collection empowers haploid genetics in human cells', Nature Methods, vol. 10, no. 10, pp. 965-971. https://doi.org/10.1038/nmeth.2609

TY - JOUR

T1 - A reversible gene trap collection empowers haploid genetics in human cells

AU - Bürckstümmer, Tilmann

AU - Banning, Carina

AU - Hainzl, Philipp

AU - Schobesberger, Richard

AU - Kerzendorfer, Claudia

AU - Pauler, Florian M.

AU - Chen, Doris

AU - Them, Nicole

AU - Schischlik, Fiorella

AU - Rebsamen, Manuele

AU - Smida, Michal

AU - De La Cruz, Ferran Fece

AU - Lapao, Ana

AU - Liszt, Melissa

AU - Eizinger, Benjamin

AU - Guenzl, Philipp M.

AU - Blomen, Vincent A.

AU - Konopka, Tomasz

AU - Gapp, Bianca

AU - Parapatics, Katja

AU - Maier, Barbara

AU - Stöckl, Johannes

AU - Fischl, Wolfgang

AU - Salic, Sejla

AU - Taba Casari, M. Rita

AU - Knapp, Sylvia

AU - Bennett, Keiryn L.

AU - Bock, Christoph

AU - Colinge, Jacques

AU - Kralovics, Robert

AU - Ammerer, Gustav

AU - Casari, Georg

AU - Brummelkamp, Thijn R.

AU - Superti-Furga, Giulio

AU - Nijman, Sebastian M.B.

PY - 2013/10

Y1 - 2013/10

N2 - Knockout collections are invaluable tools for studying model organisms such as yeast. However, there are no large-scale knockout collections of human cells. Using gene-trap mutagenesis in near-haploid human cells, we established a platform to generate and isolate individual 'gene-trapped cells' and used it to prepare a collection of human cell lines carrying single gene-trap insertions. In most cases, the insertion can be reversed. This growing library covers 3,396 genes, one-third of the expressed genome, is DNA-barcoded and allows systematic screens for a wide variety of cellular phenotypes. We examined cellular responses to TNF-α, TGF-β, IFN-γ and TNF-related apoptosis-inducing ligand (TRAIL), to illustrate the value of this unique collection of isogenic human cell lines.

AB - Knockout collections are invaluable tools for studying model organisms such as yeast. However, there are no large-scale knockout collections of human cells. Using gene-trap mutagenesis in near-haploid human cells, we established a platform to generate and isolate individual 'gene-trapped cells' and used it to prepare a collection of human cell lines carrying single gene-trap insertions. In most cases, the insertion can be reversed. This growing library covers 3,396 genes, one-third of the expressed genome, is DNA-barcoded and allows systematic screens for a wide variety of cellular phenotypes. We examined cellular responses to TNF-α, TGF-β, IFN-γ and TNF-related apoptosis-inducing ligand (TRAIL), to illustrate the value of this unique collection of isogenic human cell lines.

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U2 - 10.1038/nmeth.2609

DO - 10.1038/nmeth.2609

M3 - Article

C2 - 24161985

AN - SCOPUS:84884903662

SN - 1548-7091

VL - 10

SP - 965

EP - 971

JO - Nature Methods

JF - Nature Methods

IS - 10

ER -

A reversible gene trap collection empowers haploid genetics in human cells

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