Prion Protein is Expressed on Long-term Repopulating Hematopoietic Stem Cells and is Necessary for their Self-renewal
Author(s)Lodish, Harvey F.; Zhang, Cheng Cheng; Steele, Andrew D.; Lindquist, Susan L.
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 self-renewal.
Molecular Engineering of Biological and Chemical Systems (MEBCS);
Prion Proteins, PrP, hematopoietic stem cells, bone marrow cells