TY - JOUR
T1 - Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential
AU - Ye, Min
AU - Iwasaki, Hiromi
AU - Laiosa, Catherine V.
AU - Stadtfeld, Matthias
AU - Xie, Huafeng
AU - Heck, Susanne
AU - Clausen, Bjorn
AU - Akashi, Koichi
AU - Graf, Thomas
N1 - Funding Information:
We thank Dr. Irmgard Forster for the generous supply of the lysozyme Cre mice before their publication; Dr. Frank Costantini for the ROSA EYFP reporter and the beta actin Cre mice; Dr. Matt Thomas for the CD19 Cre mice; and Dr. Harris Goldstein for the SCID mice. Special thanks to Dr. Kelly McNagny for important suggestions. Thanks also to Drs. Betty Diamond, Matty Scharff, Steve Porcelli, and Liise-anne Pirofski for discussions, and Dr. David Traver for comments on the manuscript. This work was supported by NIH grants RO1 CA89590-01 and RO1 NS43881-01 to T.G., a Boehringer Ingelheim predoctoral fellowship for M.S., and NIH grants DK050654, DK061320, and CA072009 and a Damon-Runyon Cancer Research grant to K.A.
PY - 2003/11
Y1 - 2003/11
N2 - Single cell PCR studies showed that hematopoietic stem cells (HSCs) express a variety of lineage-affiliated genes. However, it remains unclear whether these cells exhibiting "lineage priming" represent bona fide stem cells or a subpopulation earmarked for differentiation. Here we have used a Cre-Lox approach to follow the fate of cells expressing a lineage-affiliated marker. We crossed lysozyme Cre mice with yellow fluorescent protein (EYFP) reporter mice and found EYFP gene expression not only in myelomonocytic cells but also in a fraction of HSCs as well as B cells and T cells. Transplantation of EYFP+ HSCs into primary and secondary recipients generated mice in which all hematopoietic cells were EYFP+. In contrast, crosses between CD19 Cre and lck Cre mice with reporter mice showed no EYFP expression in HSCs or intermediate progenitors. Our results demonstrate that lysozyme expression does not mark myeloid commitment and that long-term repopulation potential is maintained in primed HSCs.
AB - Single cell PCR studies showed that hematopoietic stem cells (HSCs) express a variety of lineage-affiliated genes. However, it remains unclear whether these cells exhibiting "lineage priming" represent bona fide stem cells or a subpopulation earmarked for differentiation. Here we have used a Cre-Lox approach to follow the fate of cells expressing a lineage-affiliated marker. We crossed lysozyme Cre mice with yellow fluorescent protein (EYFP) reporter mice and found EYFP gene expression not only in myelomonocytic cells but also in a fraction of HSCs as well as B cells and T cells. Transplantation of EYFP+ HSCs into primary and secondary recipients generated mice in which all hematopoietic cells were EYFP+. In contrast, crosses between CD19 Cre and lck Cre mice with reporter mice showed no EYFP expression in HSCs or intermediate progenitors. Our results demonstrate that lysozyme expression does not mark myeloid commitment and that long-term repopulation potential is maintained in primed HSCs.
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U2 - 10.1016/S1074-7613(03)00299-1
DO - 10.1016/S1074-7613(03)00299-1
M3 - Article
C2 - 14614856
AN - SCOPUS:0344276481
SN - 1074-7613
VL - 19
SP - 689
EP - 699
JO - Immunity
JF - Immunity
IS - 5
ER -
