Development of an model to study clonal lineage relationships in hematopoietic cells using mice.

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 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 B- and T-cell development.