How Faithful Flt3-Cre Mouse is to Hematopoietic Lineage Tracing?

Flt3 gene expression is known to occur at a specific development stage of hematopoiesis in mice. Flt3-Cre reporter mice have been utilized in lineage tracing studies. This review systematically evaluates different Flt3-Cre reporter constructs, focusing on labeling efficiency and consistency with endogenous Flt3 expression patterns. We discuss the strengths and limitations associated with employing marker gene expression in lineage tracing. Furthermore, this lineage tracing strategy is compared with clonal tracing strategies such as barcoding and single-cell transplantation. Finally, we propose comparing hematopoietic stem cells identified by barcoding with those identified by transplantation to know the relationship between HSCs in non-stress and stress conditions. HIGHLIGHTS: • Flt3-Cre reporter mice are excellent models to understand hematopoiesis but may not necessarily reflect endogenous expression of Flt3. • The labeling efficiency significantly differs among the Flt3-Cre reporter mice.