Leucine-rich repeat-containing G-protein-coupled Receptor 5 marks short-term hematopoietic stem and progenitor cells during mouse embryonic development

TY - JOUR

T1 - Leucine-rich repeat-containing G-protein-coupled Receptor 5 marks short-term hematopoietic stem and progenitor cells during mouse embryonic development

AU - Liu, Donghua

AU - He, Xi C

AU - Qian, Pengxu

AU - Barker, Nick

AU - Trainor, Paul A

AU - Clevers, Hans

AU - Liu, Huiwen

AU - Li, Linheng

N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2014/8/22

Y1 - 2014/8/22

N2 - 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.

AB - 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.

KW - Animals

KW - Base Sequence

KW - DNA Primers

KW - Embryonic Development

KW - Hematopoietic Stem Cells

KW - Leucine

KW - Liver

KW - Mice

KW - Real-Time Polymerase Chain Reaction

KW - Receptors, G-Protein-Coupled

U2 - 10.1074/jbc.M114.568170

DO - 10.1074/jbc.M114.568170

M3 - Article

C2 - 24966324

SN - 0021-9258

VL - 289

SP - 23809

EP - 23816

JO - The Journal of biological chemistry

JF - The Journal of biological chemistry

IS - 34

ER -