Mds1 CreER , a New Inducible Cre Allele Specific to Adult-Repopulating Hematopoietic Stem Cells

Hematopoietic ontogeny consists of two broad programs: an initial hematopoietic stem cell (HSC)-independent program arising from the yolk sac followed by HSC-dependent hematopoiesis arising from intra-embryonic arteries. While HSC-independent erythro-myeloid (EMP) progenitors and rare lymphoid progenitors, as well as HSCs, sequentially seed the fetal liver and generate blood cells, the transition from HSC-independent to HSC-derived hematopoiesis remains poorly characterized. To help resolve this question, we developed Mds1CreER mice, which inducibly express Cre-recombinase specifically in HSCs. Our lineage tracing studies indicate that HSC-derived progeny significantly expand in the liver between E14.5-E16.5. Additionally, we find that HSCs contribute the majority of F4/80+ macrophages in adult spleen and marrow, in contrast to their limited contribution to macrophage populations in brain, liver and lungs. The Mds1CreER mouse model will be useful to deconvolute the complexity of hematopoiesis as it unfolds in the embryo and functions postnatally.