Zeitschriftenaufsatz
|
2021
A genome-wide library of MADM mice for single-cell genetic mosaic analysis
Autor:in
Contreras, Ximena; Amberg, Nicole; Davaatseren, Amarbayasgalan; Hansen, AH; Sonntag, Johanna; Andersen, L.; Bernthaler, T.; Streicher, Carmen; Heger, Anna; Johnson, Randy; Schwarz, Lindsay; Luo, Liqun; Ruelicke, Thomas; Hippenmeyer, Simon
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
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.
Schlagwörter
SISTER-CHROMATID SEGREGATION; DOUBLE MARKERS; STEM-CELLS; MITOTIC RECOMBINATION; DISTINCT; COMPETITION; GROWTH; HETEROZYGOSITY; NEUROGENESIS; SPECIFICITY
Dokumententyp
Originalarbeit
CC Lizenz
CCBYNCND
Open Access Type
Gold
ISSN/eISSN
2211-1247 -
10.1016/j.celrep.2021.109274
WoS ID
PubMed ID