RT Journal Article
SR Electronic
T1 A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.05.136192
DO 10.1101/2020.06.05.136192
A1 Contreras, Ximena
A1 Davaatseren, Amarbayasgalan
A1 Amberg, Nicole
A1 Hansen, Andi H.
A1 Sonntag, Johanna
A1 Andersen, Lill
A1 Bernthaler, Tina
A1 Heger, Anna
A1 Johnson, Randy
A1 Schwarz, Lindsay A.
A1 Luo, Liqun
A1 Rülicke, Thomas
A1 Hippenmeyer, Simon
YR 2020
UL http://biorxiv.org/content/early/2020/06/06/2020.06.05.136192.abstract
AB Mosaic Analysis with Double Markers (MADM) offers a unique 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 could only be applied to <25% of all mouse genes on select chromosomes thus far. To overcome this limitation, we generated transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validated their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond proof-of-principle, we applied our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We found striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.Competing Interest StatementThe authors have declared no competing interest.