Prion Protein is Expressed on Long-term
Repopulating Hematopoietic Stem Cells and is
Necessary for their Self-renewal
Harvey F. Lodish1,2 , Cheng Cheng Zhang1, Andrew D. Steele1,2, Susan L. Lindquist1,2
1
Whitehead Institute for Biomedical Research, 2Department of Biology, Massachusetts Institute of
Technology
Abstract – We show that the prion protein (PrP) is
expressed on the surface of bone marrow cell
populations enriched in long-term repopulating
hematopoietic stem cells. Affinity purification of the
PrP-positive and PrP-negative fractions from these
populations, followed by competitive reconstitution
assays, show that all long-term repopulating
hematopoietic stem cells express PrP. Hematopoietic
stem cells from PrP null bone marrow exhibit
impaired self-renewal in serial competitive
transplantation
experiments,
and
premature
exhaustion when exposed to cell cycle-specific
myelotoxic injury. Therefore, PrP is a novel marker
for hematopoietic stem cells and regulates their selfrenewal.