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Hematopoietic stem cells maintain the homeostasis of all blood cell progeny during development and repopulation-demanding events. To study the lineage relationships during hematopoiesis, increasingly complex cell tracing models are being developed. In this study, we describe adaptations to the original  R26R-Confetti  mouse model, which subsequently offers a relatively easy approach to study low complexity clonality during hematopoiesis, with special focus on B and T lymphocyte development. This protocol employs spatiotemporal Cre expression controlled by gammaretroviral transduction for efficient fluorescent protein cell marking. Transplantation of fluorescently marked Lin -  cKit +  hematopoietic progenitor cells into Rag1 -/-  mice, resulted in the visualization of differentially contributing stem cell clones to various lineages. Our methodology is useful to study questions in fundamental and preclinical hematopoietic research and  in vivo  B- and T-cell development.

Development of an in vivo model to study clonal lineage relationships in hematopoietic cells using Brainbow2.1/Confetti mice