First Author | Contreras X | Year | 2021 |
Journal | Cell Rep | Volume | 35 |
Issue | 12 | Pages | 109274 |
PubMed ID | 34161767 | Mgi Jnum | J:306183 |
Mgi Id | MGI:6715489 | Doi | 10.1016/j.celrep.2021.109274 |
Citation | Contreras X, et al. (2021) A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Rep 35 |
abstractText | 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. |