Leucine-rich Repeat-containing G-protein-coupled Receptor 5 Marks Short-term Hematopoietic Stem and Progenitor Cells during Mouse Embryonic Development

Background: Lgr5 was shown to mark proliferating stem cells in several adult organs. Results: Lgr5 expression was detected in proliferating hematopoietic stem and progenitor cells (HSPCs) at the early stage of hematopoiesis. Conclusion: Lgr5 marks short-term (ST) hematopoietic stem and progenitor cells during the embryonic and fetal hematopoiesis. Significance: Extending Lgr5 as a HSPC marker into the hematopoietic system during development. Lgr5 is a marker for proliferating stem cells in adult intestine, stomach, and hair follicle. However, Lgr5 is not expressed in adult hematopoietic stem and progenitor cells (HSPCs). Whether Lgr5 is expressed in the embryonic and fetal HSPCs that undergo rapid proliferation is unknown. Here we report the detection of Lgr5 expression in HSPCs in the aorta-gonad-mesonephros (AGM) and fetal liver. We also found that a portion of Lgr5(+) cells expressed the Runx1 gene that is critical for the ontogeny of HSPCs. A small portion of Lgr5(+) cells also expressed HSPC surface markers c-Kit and CD34 in AGM or CD41 in fetal liver. Furthermore, the majority of Lgr5(+) cells expressed Ki67, indicating their proliferating state. Transplantation of fetal liver-derived Lgr5-GFP(+) cells (E12.5) demonstrated that Lgr5-GFP(+) cells were able to reconstitute myeloid and lymphoid lineages in adult recipients, but the engraftment was short-term (4-8 weeks) and 20-fold lower compared with the Lgr5-GFP(-) control. Our data show that Lgr5-expressing cells mark short-term hematopoietic stem and progenitor cells, consistent with the role of Lgr5 in supporting HSPCs rapid proliferation during embryonic and fetal development