A genome-wide library of MADM mice for single-cell genetic mosaic analysis

Contreras, Ximena; Amberg, Nicole; Davaatseren, Amarbayasgalan; Hansen, Andi H; Sonntag, Johanna; Andersen, Lill; Bernthaler, Tina; Streicher, Carmen; Heger, Anna-Magdalena; Johnson, Randy L.; Schwarz, Lindsay A.; Luo, Liqun; Rülicke, Thomas; Hippenmeyer, Simon

A genome-wide library of MADM mice for single-cell genetic mosaic analysis

Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.

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DOI

10.1016/j.celrep.2021.109274

Journal Article | Published | English

Scopus indexed

Author

Contreras Paniagua, Ximena^ISTA; Amberg, Nicole^ISTA ; Davaatseren, Amarbayasgalan^ISTA; Hansen, Andi H^ISTA; Sonntag, Johanna^ISTA; Andersen, Lill; Bernthaler, Tina; Streicher, Carmen^ISTA; Heger, Anna-Magdalena^ISTA; Johnson, Randy L.; Schwarz, Lindsay A.; Luo, Liqun
All

Department

Hippenmeyer Group
Sweeney Group
Pre-Clinical Facility

Grant

Molecular Mechanisms of Radial Neuronal Migration
Molecular Mechanisms of Cerebral Cortex Development
Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development

Abstract

Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.

Publishing Year

2021

Date Published

2021-06-22

Journal Title

Cell Reports

Acknowledgement

We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.

Acknowledged SSUs

Imaging & Optics Facility
Lab Support Facility
Pre-Clinical Facility

Volume

Issue

Article Number

109274

eISSN

22111247

IST-REx-ID

9603

Cite this

Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12). doi:10.1016/j.celrep.2021.109274

Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274

Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.

X. Contreras et al., “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.

Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press, 2021, doi:10.1016/j.celrep.2021.109274.

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